In rats the development of one-trial tolerance to the analgesic action of i.p. administered morphine is disrupted by the postadministration of apomorphine (30 mg/kg at 5 min but not at 3 h) or alpha-methyl-p-tyrosine (200 mg/kg at 5 min and 3 h but not at 12 h). Diethyldithiocarbamate or propranol has no disruptive effect. It is suggested that development of tolerance to the analgesic effects of morphine is mediated by sequential time-dependent biochemical processes.