Itraconazole, a new oral triazole antifungal agent, was administered in 75 courses to patients with chronic coccidioidomycosis at dosages of 50 to 400 mg/day for a median duration of 10 months. Assessment of efficacy was made with a standardized scoring system. Responses were seen in 42 of 58 assessable courses (72%). Nonresponse occurred exclusively in patients who had failed previous therapy and was most common in pulmonary disease. Toxicity was minimal at the doses studied. Pharmacokinetic analysis of itraconazole in serum at steady state showed negligible circadian variation; differences in serum concentrations among patients were large. Clinical isolates of Coccidioides immitis showed uniform in vitro susceptibility to itraconazole. Itraconazole shows impressive activity in this series of patients with refractory coccidioidomycosis. Further evaluation of itraconazole in this and in other systemic mycoses is in order.