Pharmacotherapy response was compared in 94 cocaine-abusing methadone patients with (n = 75) and without (n = 19) antisocial personality disorder (ASP), in a 12-week, randomized, double-blind trial using desipramine 150 mg daily (n = 30), amantadine 300 mg daily (n = 33), and placebo (n = 31). Retention was lower for the ASP group (ASP 9.6 weeks vs. non-ASP 11.2 weeks). During the first 2 weeks, there was no significant difference in the percentage of cocaine-free urines between the ASP vs. non-ASP patients (9% vs. 18%), but during the last 2 weeks, the non-ASP patients showed a significantly greater percentage of cocaine-free urines (30% vs. 7%). Placebo-treated patients in both groups demonstrated no significant difference in their urine toxicologies comparing the first to the last two weeks of treatment. However, the percentage of cocaine-free urines increased from 15% to 32% in medicated non-ASP patients, but showed no change in medicated ASP patients. Thus, antisocial personality disorder was a poor prognostic factor for treatment retention and continued cocaine abuse, and medication did not improve treatment outcome for the ASP patients, but did for the non-ASP patients.