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. This work is performed in collaboration with other members of the Dept. Pharmaceutical Sciences, University of Maryland School of Pharmacy, namely Dr. Alex MacKerell (Molecular Modeling), Dr. Natalie Eddington (pharmacokinetics), and Dr. Rae Matsumoto (Pharmacology, West Virginia). We gratefully acknowledge NIDA (DA-13583) for funds.