In an attempt to characterize a possible drug interaction between methadone and disulfiram, 500 mg/day insulfiram was administered orally for seven days to seven subjects on methadone maintenance. Plasma methadone concentrations and urinary excretion of methadone and its pyrrolidine and pyrrolidone metabolites were measured and subjective symptoms of opiate intoxication and abstinence were noted before, during, and after disulfiram administration. Mean trough plasma methadone concentrations and terminal half-lives were lowest and shortest during disulfiram treatment, although this finding was not statistically significant. The ratio of urinary methadone to its pyrrolidine metabolite decreased during disulfiram treatment in all subjects. There is no evidence to support our original hypothesis that disulfiram might inhibit methadone metabolism. In contrast, urinary excretion of the major pyrrolidine metabolite increased relative to excretion of methadone. This suggests enhanced N-demethylation during disulfiram treatment. Disulfiram had no effect on opiate intoxication or abstinence symptoms. Disulfiram may alter methadone disposition, but in this study it was shown that in doses used for management of alcoholism there was no significant interaction between disulfiram and methadone.