To investigate possible causes for the significantly increased incidence of sepsis observed in galactosemic neonates, the in vitro effect of galactose on neutrophil function in healthy newborns was studied. Neutrophils from 25 normal newborns and 23 normal adult volunteers were incubated with 100 mg of glucose per dl, 300 mg of galactose per dl and 300 mg of galactose plus 100 mg of glucose per dl, respectively. Tests for neutrophil function included chemiluminescence (CL), chemotaxis (CTX) and adherence. Neutrophil CL (measure of bactericidal activity) was significantly depressed by galactose in both adults (30.2%) and newborns (59.5%); however, neonatal neutrophil function (CL) was depressed to a much greater extent than in adults. CTX was also significantly depressed by galactose in newborns but not in adults. Supplementing the galactose-containing medium with glucose restored both CL and CTX function to normal in adults. However, only CTX was restored in newborns, while CL remained markedly depressed. Neutrophil adhesion, a function which is not energy-dependent, was not affected by galactose in both adults and newborns. These findings indicate that depressed neutrophil function by galactose or its metabolites may contribute to the high incidence of sepsis in galactosemic neonates.