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In the neonate, fungal infections result in significant morbidity and mortality. For very low birth weight (less than 1,500 g) infants, we prospectively determined the fungal colonization rate to be 26.7%. In one third of infants with fungal colonies, mucocutaneous candidiasis developed, and in 7.7%, systemic disease developed. Two thirds of the infants had colonies in the first week of life. This colonization was probably acquired during labor and delivery, because those infants who had colonization were more often delivered vaginally than by cesarean section. Early colonization, commonly from the gastrointestinal or respiratory tract, featured Candida albicans and Candida tropicalis. Late colonization, occurring after 2 weeks of life (15.0% of patients), was more likely to be cutaneous and was associated with either Candida parapsilosis or such poor growth that the organism could not be identified. Infants with colonization only rarely had budding yeasts (6.1%), whereas more than half of the infants with either a urinalysis showing budding yeasts or a urine culture growing fungi had invasive disease. Fungal contamination was not found on either thoracotomy tubes or catheter tips. In the low birth weight infant, fungal colonization represents a significant risk factor for cutaneous or systemic candidiasis in these infants.