During the 4-year period February 1989 to January 1993, 13 premature babies aged 1-21 days and with congenital syphilis were admitted to the National Cheng Kung University Hospital. Of the 13 premature infants, 8 (62%) had unusual desquamation over palms and soles. Bone changes with periosteal reaction and/or metaphyseal dystrophy were observed in 11 cases (85%). Three mothers were diagnosed as being infected during pregnancy; 2 were treated with penicillin. The clinical features of congenital syphilis in premature neonates are somewhat different from those previously reported. Bone changes, hepatosplenomegaly, respiratory distress, skin lesions, especially over the soles and palms, cerebrospinal fluid abnormalities, and jaundice were the major manifestations in our series. In premature infants with these symptoms and signs, congenital syphilis should be considered as one of the differential diagnoses. Once the diagnosis of congenital syphilis is made, adequate penicillin therapy should be given.