Our NIH funded medicinal chemistry research program in the area of opioids involves the design and synthesis of novel opioids as potential analgesics with reduced undesired effects, specifically analgesic tolerance, and also to investigate the interaction of the opioid system with other biological systems. In the area of antidepressants, we are focused on delineating the influence of the cholinergic system in depression in collaboration with Dr. James Woods. We gratefully acknowledge NIDA, NIMH, and TEDCO for funds.