The risk of relapse into frequent heroin use was studied among 732 participants of the Amsterdam Cohort Study (ACS) on HIV/AIDS among drug users, who experienced an episode of abstinence from or occasional use of heroin. Participants of the ACS were recruited primarily from easy access ("low-threshold") methadone programs. The duration of abstinence/occasional use and relative risks (RR) of relapse were estimated by analyzing 1577 episodes by means of survival analysis using characteristics of patients and methadone treatment as covariates. The majority of episodes (85.8%) were followed by relapse within 5 years. Less education, intense use of heroin prior to the episode of abstinence or well-controlled use, occasional use of heroin and intense use of cocaine during the episode, and having a drug-using partner or having no partner were significantly associated with a higher risk of relapse. Among frequent attendees of a "low-threshold" methadone program, relapse was associated with the daily dose of methadone: RR for dosages <40 and 40-60 mg, compared with doses of >100mg, were 1.45 (P<0.01) and 1.59 (P<0.01), respectively. No beneficial influence was revealed of methadone dosage or program attendance in itself on the risk of relapse into cocaine. High doses of methadone in a harm-reduction setting extend the duration of an episode of no or occasional use of heroin. Other factors, such as no occasional use of heroin during the episode, no use of cocaine, and having a non-using partner, seem to be equally important.