Cord blood monocyte synthesis of IL-1 was investigated by using a thymocyte proliferation assay. Monocytes from 27 infants ranging in gestation from 31 to 41 weeks (mean 38.9, SE 0.54) with birthweights from 1.20 to 4.31 kg (mean 3.24, SE 0.13) were isolated from cord blood; 2 x 10(5) cells/ml were plated in 15 mm wells and stimulated with 10 micrograms/ml LPS (E. coli). Control cultures contained medium alone. Supernatants were harvested after 24 hr and tested in a C3H/HeJ mouse thymocyte proliferation assay. The mean response for 27 cord monocyte samples at 24 hr was 14,142 cpm (SE 1,499), not significantly different than that for cells obtained from eight normal adult volunteers (15,137 cpm, SE 3,535). Vaginally delivered infants with perinatal complications such as amnionitis, fetal distress, or early sepsis had significantly increased unstimulated activity (5,139 vs 1,331 cpm) compared to samples from normal infants, whereas stimulated activity was not significantly different (16,219 vs 12,261 cpm). Thus, the IL-1 response to lipopolysaccharide is intact in newborn human monocytes and there is evidence of an increased unstimulated activity following neonatal complications.