Two fatal cases of cryptococcal meningitis complicating adrenocorticosteroid-treated systemic lupus erythermatosus are reported. In one patient who was treated with flucytosine alone, after an initial period of improvement cryptococci resistant to flucytosine were isolated, and subsequent amphotericine B treatment silated, and subsequent amphotericin B treatment did not alter the progress of the disease. In the second patient, who received both drugs concurrently, resistant cryptococci did not appear and the patient recovered sufficiently to return home. Flucytosine-resistant mutants could be demonstrated in vitro in the original cryptococcal isolated from both patients. The use of flucytosine and amphotericin B in combination is discussed.