Fluconazole was administered at doses of 50-400 mg/d to 18 patients (15 men, three women) with coccidioidal meningitis. After a mean duration of treatment of 9.8 months, 10 (67%) of 15 assessable patients had responded, one (7%) of 15 had partially responded, and four (27%) of 15 had not responded to therapy. Five (63%) of eight assessable patients receiving fluconazole as sole therapy responded or partially responded. Two patients discontinued fluconazole after initially responding to therapy, and both experienced relapse. The toxicity of fluconazole remains minimal at doses to 400 mg/d. The penetration of fluconazole into cerebrospinal fluid is substantial at all doses studied. Thus fluconazole continues to show promise even as sole therapy against coccidioidal meningitis. Not all patients respond, however, and relapse may be a problem with the currently studied doses and durations of therapy.