OBJECTIVE To evaluate the efficacy and safety of CHQ in a combination treatment with ZDV/ddI in HIV-1-infected children. METHODS Fifty five HIV-infected children were randomly enrolled into 3 treatment groups: (I) ZDV + ddI (n = 25); and (II) ZDV + ddI + CHQ (n = 21); and (III) ZDV + ddI experienced children were non-randomly added CHQ (n = 9). Weight, CD4+ T-lymphocytes and plasma HIV-RNA were measured at weeks 0, 8 and 24. RESULTS Fifteen, 16 and 8 children from Groups I, II and III were evaluated. No significant improvement in the mean Z-score for weight in groups I and II, but a decrease occurred in group III after 6 months of therapy. In group I, II and III, the respective change in the mean CD4+ T-lymphocyte percentage was +6.7, +4.0 and -0.6. The decrease in the plasma HIV-RNA log was 0.9, 1.1 and 0.7, respectively. There was a trend for more nausea/vomiting in group II/III and more opportunistic infections in group III. CONCLUSIONS 1. The addition of chloroquine in ZDV/ddI regimen provided no significant improvement in clinical, immunological and virological parameters. 2. Chloroquine induced immunosuppression and nausea complicated its use.