In the present study, the effects of histamine on naloxone-induced jumping in the presence or absence of adrenoceptor or acetylcholine receptor antagonists in morphine-dependent mice were examined. In these experiments, the drugs were used before s.c. injection of naloxone (2 mg/kg), to test their effects on the expression of jumping. The i.c.v. administration of histamine (5-20 microg/mouse) 15 min before naloxone injection decreased the number of jumps in mice. When the histamine H(2) receptor antagonist, cimetidine (5-20 mg/kg), and the histamine H(1) receptor antagonist, pyrilamine (5-20 mg/kg), were administered i.p. to morphine-dependent mice, only cimetidine enhanced the jumping behaviour. Administration of cimetidine (20 mg/kg, i.p.), 30 min, of the beta-adrenoceptor antagonist, propranolol (2.5-10 mg/kg, i.p.), 15 min but not of pyrilamine (20 mg/kg, i.p.), 30 min before naloxone injection, decreased the histamine effect. The i.p. administration of an acetylcholine receptor antagonist, atropine (5 and 10 mg/kg, i.p.), the alpha(1)-adrenoceptor antagonist, prazosin (0.5, 1 and 2 mg/kg, i.p.), and alpha(2)-adrenoceptor antagonist, yohimbine (0.5, 1 and 2 mg/kg, i.p.), 15 min before naloxone injection, had no effect on the histamine response. Single administration of propranolol, atropine or prazosin decreased, while yohimbine increased the naloxone-induced jumping. It is concluded that the histamine H(2) receptor mechanism may be involved in the influence of histamine on the expression of naloxone-induced jumping in morphine-dependent mice.