OBJECTIVES: This study examined two major methadone treatment factors, visit frequency and methadone dose, posited to be important in reducing intravenous drug use and human immunodeficiency virus (HIV) transmission. METHODS: One hundred fifty opiate-dependent subjects randomly assigned to four groups received 50 or 80 mg of methadone and attended a clinic 2 or 5 days per week. RESULTS: Survival analysis indicated higher dropout rates for groups having five vs two visits per week (Chi2=7.76). Higher proportions of opiate-positive results on urine screens were associated with lower methadone doses (F[1,91]=4.74). CONCLUSIONS: Receiving take-home doses early in treatment enhanced treatment retention. The 50-mg dose combined with five visits per week produced the worst outcome. Fewer visits enhanced retention at 50 mg, but opiate use rates were higher at this dose than they were for either 80-mg group. The HIV infection rate at entry was 9%. No subjects seroconverted during the study. Risk behaviors for acquired immunodeficiency syndrome declined over time regardless of group/dose assignment. These results have important implications for modification of regulatory and clinic policy changes.