This study describes the relationship between the need for psychiatric consultation, illicit drug use, and zidovudine (AZT) adherence in HIV-infected injection drug users (IDUs) in methadone maintenance treatment (MMT). The treatment records of 57 IDUs in MMT who had been prescribed AZT between May and August of 1991 were reviewed. Those who required psychiatric consultation (P+,N= 46, 81%) were compared with those who did not require psychiatric consultation (P-,N= 11, 19%) on adherence to AZT treatment (using the mean corpuscular volume [MCV] as a biological marker), on recent illicit drug use, and on CD4 lymphocyte (T cell) count changes from the beginning to the end of AZT treatment. The P+ subjects were less likely than P- subjects to adhere to AZT treatment: fewer in the P+ group had an MCV outside of the normal range, and P+ subjects had a lower average monthly increase in MCV since the beginning of AZT treatment. Recent illicit drug use and CD4 lymphocyte count changes from the beginning to the end of AZT treatment did not show group differences. Psychiatric morbidity among HIV-infected IDUs in MMT is common, and may contribute to poor adherence to AZT treatment. Psychiatric screening and adherence-enhancing interventions should be targeted to IDUs entering drug treatment programs.