TPN-associated cholestasis (TPNAC) is a common problem in neonatal surgical patients. Of the 222 infants admitted to the neonatal surgical intensive care unit between January 1982 and June 1983, 46 patients received parenteral nutrition for over 14 days. Cholestasis occurred in 16 of these patients (35%), while 30 patients remained jaundice-free. Clinical characteristics associated with the development of TPNAC, included primary diagnosis, low birth weight, duration of TPN administration, the interval before enteral feeding was initiated, sepsis, central venous catheter infection, and the number of operative procedures. Factors which did not appear significant in the development of conjugated hyperbilirubinemia were prematurity, sex, gestational age, average daily weight gain, and the specific components of the nutritional intake. Mortality was high in the children with cholestasis (31%) as compared to the "normal" neonates (3%) and two of the five deaths were directly related to progressive hepatic dysfunction. This report confirms the high incidence of TPNAC in the newborn surgical population and discusses the critical risk factors associated with development of the syndrome.