The clinical courses in 27 infants with culture or autopsy evidence of systemic candidiasis were reviewed. Twenty-two infants (group 1) had persistent signs of sepsis and clinical deterioration or died before institution of antifungal therapy. Five infants (group 2) improved markedly before culture results were reported, and recovered without systemic antifungal therapy. Fourteen infants in group 1 (64%) had central nervous system infection. Of four patients in whom CNS involvement was diagnosed only postmortem, antemortem cerebrospinal fluid from three was abnormal despite sterile cultures; no antemortem CSF was obtained in the other. In meningitis caused by susceptible organisms addition of flucytosine sterilized CSF within 5 days, although prior amphotericin monotherapy had been unsuccessful. Of 14 patients in group 1 who received systemic antifungal therapy, only one died with Candida infection. Toxicity from antifungal agents occurred in 11 of 13 successfully treated infants, but was reversible in every case except one by modifying the dosage. Our data indicate that (1) CNS infection is very common in infants with systemic candidiasis, (2) combined flucytosine-amphotericin therapy may facilitate treatment of CNS infection and should be the initial therapy for systemic candidiasis in infants, (3) Gram stains of CSF and urine enhance early diagnosis, (4) isolation of Candida from normally sterile body fluids in high-risk infants should be considered pathogenic and therapy initiated unless the clinical course strongly suggests otherwise, and (5) toxicity from antifungal agents is common but usually reversible.