Previous reports in the literature have documented that systemic infection with Candida albicans in very premature infants is frequently fatal (54%) or associated with significant morbidity in survivors (25%). Five patients with a mean birth weight of 829 g had a diagnosis of systemic candidiasis during their stay in a newborn intensive care unit. All infants survived with minimal sequelae following aggressive early treatment with amphotericin B and 5-flucytosine. A review of these five extremely premature infants and 26 previously reported patients suggests the following: (1) disseminated candidiasis is common in the absence of positive findings in blood, CSF, and/or urine cultures; (2) transient candidemia rarely resolves without therapy; (3) meningitis and osteoarthritis occur more frequently than in older patients with disseminated disease; and (4) premature infants tolerate amphotericin B and 5-flucytosine well. Infants who are found to have systemic cultures positive for candidiasis should be treated by (1) removing all factors that predispose to systemic candidiasis (eg, indwelling catheters, broad-spectrum antibiotics); (2) early initiation of systemic antifungal therapy with amphotericin B and 5-flucytosine; and (3) searching for additional foci of disease. After the disease is recognized and treatment is prompt and aggressive, outcome can be substantially improved.