This volume contains the proceedings of the third in a series of conferences entitled, The International Symposium on Biological Reactive Intermediates. The first was held at the University of Turku in Finland, in 1975, the second at the University of Surrey in the United Kingdom, in 1980 and the most recent at the University of Maryland in the United States, in 1985. The significance of these conferences has been emphasized by the rapid growth of mechanistic toxicology over the last decade. These conferences were initially stimulated by the attempt to uncover the significance behind the observations that the toxicity of carcinogenic responses produced by many chemicals was associated with the observation that their metabolism led to the formation of chemcially reactive electrophiles which covalently bound to.nucleophilic sites in cells such as proteins, nucleic acid or fats.

Recently, newer concepts have arisen which have necessitated the expansion of subjects covered by the conference. For example, the application of newer knowledge of the role of active oxygen species in reactive metabolite formation, the concept of suicide substrates, examination of the function of glutathione in cells, application of immunological techniques and molecular biological probes to the solution of toxicological problems all had an impact on the study of the biological reactive intermediates. Many workers in the field are now asking questions such as: What is the meaning of covalent bonding of reactive metabolites to proteins? How does covalent binding of reactive metabolites to DNA pave the way for a carcinogenic response? What role does genetics play in determining toxicological responses? These and other questions were raised at the symposium.

The study of biological reactive intermediates began with the pathfinding observations of Betty and Jim Miller of the McArdle Institute of the University of Wisconsin, and it is to them that this symposium was dedicated. They have played an important role in previous symposia in this series. They are not people who readily sit back on their laurels and accept acclaim. At the symposium each made a major presentation, they both attended every session and they were among the most active questioners. Their overall contribution to the symposium helped to insure that the scientific quality of the discussions was excellent and the meeting was an exciting intellectual adventure. We must thank them for all that they have contributed to our understanding of these phenomena, as well as, for their vital contribution to this symposium.The meeting was held at the excellent facilities in the The Center for Adult Education of the University of Maryland at College Park, MD on June 6-8, 1985.

Support for the symposium came from the National Institute of Environmental Health Sciences, the U.S. Environmental. Protection Agency, Hoffmann-LaRoche, Inc., the International Society for the Study of Xenobiotics, the Drug Metabolism Section of International Union of Pharmacology, Rutgers, the State University of New Jersey, Thomas Jefferson University, the Medical University of South Carolina and the University of Maryland.The organizing committee for the conference included A.H. Conney (Hoffmann-LaRoche, Inc.), G.G. Gibson (University of Surrey), J.R. Gillettee (National Institutes of Health), D.J. Jollow (Medical University of South Carolina), J.J. Kocsis (Thomas Jefferson University), R.E. Menzer (University of Maryland), J.0. Nelson (University of Maryland), R. Snyder (Rutgers University) and C.M. Witmer (Rutgers University).

The rapid progress that has been enjoyed in the study of biological reactive intermediates in recent years means that complete coverage of the field in a brief symposium is not possible. Nevertheless, active discussion abounded and it fell upon the session chairmen to insure that time was adequate for both presenters and discussers. The highly dedicated and efficient chairmen were: G. G. Gibson (University of Surrey, Guildford), F. DeMatteis (MRC Toxicology Unit, Carshalton), P.N. Magee (Temple University, Philadelphia), D.Y. Cooper (University of Pennsylvania, Philadelphia), H. Greim (Gesellschaft fur Strahlen- and Umweltforschung MBH, Munich), D.J. Reed (Oregon State University, Corvallis), K.J. Netter (University of Marburg, Marburg), H. Kappus (Free University of Berlin, West Berlin), R. W. Estabrook (University of Texas Health Science Center, Dallas), A. Hildebrandt (Max von Pettenkofer Institute, West Berlin), H. Bolt (University of Dortmund, Dortmund).

Modern toxicology is a biological science with chemical overtones, which must ultimately explain how chemicals cause adverse changes in biological systems. As these interactions enlighten us, we will learn more about the underlying principles of life itself. In parallel, we will also apply our new knowledge to attempt to solve the problems of exposure to chemicals in the various environments and media characteristic of life in society. Thus, the small band of investigators that met in Turku in 1975 has not only grown in numbers and accomplishment but is also beginning to have an impact social policy. Of utmost importance, however, is that few if any among these researchers consciously directed their efforts at anything other than pursuing scientific knowledge, thereby enforcing the adage that the intellectual effort involved in the pursuit of excellence in science will bear fruit when properly applied.

It was a pleasure for all attendees to gather together again to continue our discussions. This group has demonstrated the ability to communicate their results to their colleagues and discuss the results in a cordial and cooperative manner which has set an example to their students, many of whom are now working in this area. We plan to continue these discussions in the future and to maintain these close scientific relationships which have potentiated our productivity.