Mu (mu) and delta (delta) opioid receptors mediate the actions of the endogenous opioid ligands, in addition to being targets for many analgesic drugs and drugs of abuse. Previous studies have suggested that these two receptor subtypes can physically interact. This thesis demonstrates that mu and delta receptors co-localize in cortical and striatal neurons of rat brain, suggesting important physiological relevance for mu-delta hetero-oligomerization. Using a time-resolved fluorescence resonance energy transfer (trFRET) assay, specific interactions between mu and delta receptors were observed representing the first description of mu-delta hetero-oligomerization at the cell surface of living cells. The trFRET method was also used to demonstrate that the site of oligomer formation is in the endoplasmic reticulum and to show that oligomeric structure was not altered by agonist treatment. trFRET was also employed to examine interactions between D1 and D2 dopamine receptors as well as a variety of Family A receptors.