Medication non-adherence in the treatment of chronic diseases compromises the effectiveness of therapy. There is little information about the extent of medication adherence or determinants of medication adherence in HIV disease, an issue of increasing importance in this new therapeutic era of combination antiretroviral therapy. We studied 244 HIV-infected medical assistance-insured patients attending an HIV hospital-based clinic regarding the extent of and predictors of adherence to antiretroviral therapy and/or Pneumocystis carinii (PCP) prophylaxis. Patients were asked to report medications being taken, patterns of use, and knowledge and attitudes about HIV therapies. Medical record report of type, dose, and frequency of medication was compared to self-report by the Kappa statistic. Urine sulfamethoxazole assay was obtained from 47 patients prescribed daily sulfamethoxazole-trimethoprim. Odds ratios (with 95% CI) were computed to assess predictors of greater than 80% adherence. Multivariate analysis was performed using logistic regression. Among patients prescribed antiretroviral therapy, 60.4% reported equal to or greater 80% adherence in the previous 7 days; 49.0% reported equal to or greater than 80% adherence with PCP prophylaxis in the previous 7 days. Seventy-nine percent of patients who reported taking daily sulfamethoxazole-trimethoprim had detectable urinary sulfamethoxazole. In multivariate analysis, greater or equal to 80% adherence to antiretroviral therapy was associated with taking medication equal to or less than twice a day (OR = 1.44, CI:1.01-1.96), being likely to take medication when not at home, (OR=1.41,CI:1.04-2.00) and positive self-efficacy(OR=1.57, CI:1.13-2.17). For PCP prophylaxis, equal to or greater than 80% adherence was associated with presence of family (OR=1.81,CI:1.17-2.78) and being likely to take medication when not at home (OR=1.45, CI:1.01-2.06). There is a relatively low level of adherence to antiretroviral therapy and PCP prophylactic regimens. Decreasing the complexity of antiretroviral regimens, and working with patients to modify identified barriers to adherence, including attitudes about efficacy, may improve effectiveness of medications and prolong survival.