In equianalgesic doses, azidomorphine is reported by J. Knoll, S. Fürst and K. Kelemen (The pharmacology of azidomorphine and azidocodeine. J. Pharm. Pharmacol. 25: 929-939, 1973) to be less likely than morphine to cause physical dependence. As the separation of the analgesic from the dependence-producing properties would represent an important contribution to the development of potent analgesic drugs, we have compared the effects of azidomorphine and morphine in a number of experiments in laboratory animals. In analgesic studies, azidomorphine was more potent than morphine in all tests and by every route of administration. However, the differences between the analgesic effects of azidomorphine and morphine were much smaller after oral than after parenteral administration. In the rhesus monkey, the programmed administration of azidomorphine over a period of 9 weeks produced physical dependence. In addition, azidomorphine was self-administered by the rhesus monkey over 3 weeks producing marked opiate-like physical dependence. It is concluded that the introduction of the azido group into the morphine molecule leads to a marked increase in analgesic activity compared with the parent drug but which does not decrease the ability to produce physical dependence.