For a 24-month period (1977 through 1978), the determinants of neonatal intensive care unit (NICU) mortality were examined retrospectively in 133 consecutively admitted newborn infants who weighed less than 1,000 g at birth. Seventy-one (53.4%) died during the first five days of life, 27 (20.3%) died after the first five days of life, and 35 (26.3%) were eventually discharged from the unit. Neonatal infection was the key determinant of increased mortality after the first five days of life. In these patients, gram-positive organisms were recovered from 54% (14/26) of all body fluid cultures from 21 infected infants. Infections included Staphylococcus epidermidis (27% [7/26]), Staphylococcus aureus (15% [4/26]), and Escherichia coli (11% [3/26]). We propose that reducing the incidence of neonatal infections is necessary to substantially improve late NICU mortality in these very-low-birth-weight neonates.