The incidence, etiology and timing of neonatal infection were assessed in a regional neonatal intensive care unit from 1983 through 1992. Infection onset was considered as very early (< 24 hours), early (1 to 7 days) or late (8 to 60 days). Case-fatality rates were determined for different weight groups and time periods (1983 to 1987 vs. 1988 to 1992). Overall neonatal sepsis incidence changed very little, but there was a marked decrease in very early onset sepsis in 1988 to 1992 especially in very low birth weight (< 1500 g) infants, possibly attributable to increased use of prenatal antibiotics. There was an accompanying increase in late onset sepsis, primarily nosocomial infection associated with improved survival of tiny infants, most striking after exogenous surfactant became readily available. During 1988 to 1992, because of very few very early-onset cases, very low birth weight infants had overall case fatality rates of about 10%, which were the same as for larger infants. The predominant organism in very early onset infection was Group B Streptococcus (GBS) (27 of 58) and in late onset infection was coagulase-negative staphylococcus (57 of 103). More cases of early onset GBS pneumonia were seen in the last 5 years. Neonatal meningitis was seen rarely during this decade, with only one case documented in the first 24 hours of life.