We undertook to determine Staphylococcus epidermidis colonization patterns and risks of sepsis in a cohort of 82 consecutive intensive care nursery admissions (birth weight 1,285 +/- 57 g), with 24 infants weighing < 1,000 g at birth. Colonization was determined by skin and stool cultures collected at three time points. Multiple neonatal variables were classified into three intervals preceding the time of sample collection including the occurrence of S. epidermidis sepsis. 16 infants (20%) developed S. epidermidis sepsis. 81% of these episodes occurred in infants < 1,000 g. Skin colonization was nearly universal at all sampling points. Rectal colonization was 63.6% initially (10 +/- 0.4 days), then declined to 32% by the third sample (37 +/- 0.4 days). Neither prevalence of skin nor rectal colonization influenced the incidence of sepsis significantly. Statistically significant risk associations for sepsis for the entire intensive care nursery population included: low birth weight, gestational age, presence of a central line, and delayed feeding. For infants < 1,000 g the occurrence of sepsis during the second study time period (54% of the episodes) was associated with preceding steroid exposure. During the third study time period, birth weight and delayed attainment of full enteral feeds showed a statistically significant association with sepsis. We conclude that infants < 1,000 g are at an increased risk of S. epidermidis sepsis. Extreme immaturity, steroid therapy, and prolonged hyperalimentation are all significant risk associations.