To study the clinical course and biochemical features of congenital syphilitic hepatitis, the records of all 22 pediatric patients admitted to North Carolina Memorial Hospital between 1969 and 1979 with a positive maternal, cord blood, or serum VDRL were reviewed. Of the seven infants identified with symptomatic congenital syphilis, five had clinical and biochemical evidence of liver dysfunction. All five were jaundiced (peak bilirubin ranged from 8.4 to 29.8 mg/dl, in each case greater than 40% conjugated). Peak transaminase elevation ranged from seven to 150 times normal. Serum glutamic-oxaloacetic transaminase exceeded serum glutamic-pyruvic transaminase in each infant, the difference ranging to 7,400 U. The onset of illness did not occur until after treatment had been initiated in two of these five cases. Liver dysfunction increased with treatment in all four infants with serial enzyme determinations. Liver dysfunction also persisted for more than 6 weeks after adequate treatment in two cases. Liver biopsy 5 weeks after treatment in another infant showed giant cell hepatitis. These observations suggest that treatment can potentiate liver dysfunction in congenital syphilis and that viable treponemes are not necessarily essential in the pathogenesis of the hepatitis.