Sixty-two premature infants less than 2,000 gm birth weight received parenteral nutrition (PN) during periods of respiratory distress with feeding intolerance. Intrahepatic cholestasis (direct bilirubin greater than or equal to 1.5 mg/dl) associated with PN developed in 14 or 23% of these infants. The mean time on PN to onset of cholestasis was 42 days, and the cholestasis persisted as long as the infants continued to receive PN. All five infants who had serial follow-up laboratory studies showed an eventual return of direct bilirubin levels to normal. The direct bilirubin level appeared to be the best clinically available test to monitor for the onset and to follow the resolution of this complication. The very low birth weight infants less than 1,000 gm appeared to be at an increased risk of developing cholestasis with an incidence of 50%. However, there was no correlation between the length of time PN was administered to onset of cholestasis and the gestational age or birth weight of the infants. These tiny premature infants also received PN for significantly longer periods of time, and the longer the infusions were administered the greater was the risk of cholestasis developing.