The objective of this prospective, noncomparative study was to assess the safety and efficacy of clindamycin and primaquine therapy for mild-to-moderate pneumocystis pneumonia (defined as a difference of < 40 mm Hg between the alveolar and the arterial oxygen determinations) in patients with AIDS. In the first part of the study, 22 patients were treated with iv clindamycin (900 mg every 8 hours) for the first 10 days, and then their therapy was switched to oral clindamycin (450 mg every 6 hours) for an additional 11 days. In the second part of the study, 38 patients were treated entirely with oral clindamycin (600 mg every 8 hours). All patients were treated with oral primaquine base (30 mg once daily). Fifty-five (92%) of 60 patients responded to the study treatment. Forty-six (77%) of 60 patients completed a full course of therapy. Of the nine patients with treatment-limiting toxic effects, four had only a mild rash. This study indicates that the combination of clindamycin and primaquine is an effective and well-tolerated therapy for mild-to-moderate pneumocystis pneumonia in patients with AIDS. Entirely oral therapy appears to be as effective as initial therapy with iv clindamycin.