The acute toxicity of heroin (3,6-diacetylmorphine, DAM) and its metabolites 6-acetylmorphine (AM) and morphine (M) following intravenous (i.v.) and intracerebroventricular (i.c.v.) administration and their tailflick-test analgesic activity following i.c.v. administration were studied in mice. After i.c.v. administration, M was 2.5-3 times more potent as a naloxone-reversible analgesic than either DAM or AM. DAM and AM provoked a naloxone-sensitive respiratory depressant lethality (i.c.v.) while M (i.c.v.), and all three drugs given i.v., caused convulsions prior to death. The dose-response and naloxone antagonism studies suggest that the receptor mechanisms which may subserve opiate convulsions differ from those mediating either analgesia or depressant lethality. Studies of DAM's disposition in vivo and in vitro suggest that unhydrolyzed DAM may contribute to its own pharmacodynamic profile after i.v., but not subcutaneous (s.c.) administration to mice.