Blood monocytes produce two well-defined cytokines, tumor necrosis factor/cachectin (TNF) and Il-1, that have multiple immunologic and inflammatory functions. This study examined the secretion of these cytokines by cord blood monocytes from preterm and term neonates stimulated with or without lipopolysaccharide (LPS). Seventeen samples (eight preterm, nine term) were collected. Supernatants of monocytes were assayed for activities of IL-1 (mitogenesis for mouse thymocytes) and TNF (cytotoxicity for L929 cells). IL-1 and TNF activities were not significant in supernatants of unstimulated monocytes from either preterm or term infants. IL-1 secretion by LPS-stimulated monocytes from term and preterm neonates was comparable to IL-1 activity by monocytes from adults, but TNF activity by LPS-stimulated monocytes from preterm neonates was significantly less than that from monocytes of either term or adult groups (p less than 0.05). TNF activity in supernatants of LPS-stimulated monocytes was neutralized 100% by monoclonal antibody to TNF-alpha; IL-1 activity was neutralized 80% by polyclonal antiserum to IL-1-beta. Given the multifactorial biologic activities of TNF, the decreased secretion of TNF by monocytes from preterm neonates may be significant in describing mechanisms for the increased susceptibility of the preterm neonate to infection.