Fluconazole is one of the new antifungal triazoles undergoing clinical trials. We used fluconazole at a dose of 50 or 100 mg/day in an open trial for the treatment of patients with persistent coccidioidomycosis. Fourteen patients were enrolled and treated for a mean of 13 +/- 7 months. Two failed to respond. Of the 12 who responded, one reactivated while being treated, and one died of myocardial infarction after successful treatment of his fungal infection; six had relapses from nine days to 15 months after treatment was stopped. Only four patients are asymptomatic at a mean of 14 +/- 3 months after cessation of treatment. Fluconazole is well tolerated at this dose. In view of its low toxicity, the partial clinical efficacy observed, and the high recurrence rate of chronic coccidioidal infection, it would be justified to try higher doses.