Malassezia furfur (Pityrosporum orbiculare, P ovale), a lipophilic yeast that is part of the normal skin flora, causes tinea versicolor but has only rarely been associated with more serious infections. We report five episodes in four infants of catheter-related infection caused by this organism. All episodes occurred in infants who had survived serious neonatal disorders and were receiving prolonged therapy with intravenous fat emulsion. Sudden onset of fever without focal findings was the usual presentation; however, one afebrile patient had recurrent episodes of apnea, bradycardia, and cyanosis. Thrombocytopenia was a prominent finding. Patients were generally treated with amphotericin B. All patients recovered when the colonized catheter was removed or fat emulsion therapy was stopped. The yeast usually grew slowly in blood culture media but grew readily when subcultured onto Sabouraud's medium coated with sterile olive oil. Yeasts were readily identified in all four patients in whom a buffy coat Gram stain was obtained of blood from the central intravenous catheter. M furfur may be a fairly common but unrecognized cause of catheter-related sepsis in infants receiving long-term fat emulsion therapy. This organism should be sought whenever routine blood cultures are negative for bacteria and yeasts are observed in a buffy coat Gram stain.