The maturation of monocyte function across gestational age is an important factor in the host response of preterm and term newborns to infectious and non-infectious agents. EGR-1 is essential in promoting cell differentiation of progenitor cells to macrophages. LPS stimulates MN immune function and EGR-1 expression. Nitric oxide modulates EGR-1 expression and induces MN differentiation. Investigating the developmental expression of EGR-1 in response to LPS and to NO is relevant to our study of development of monocyte immune responses. Freshly isolated cord blood MN and peripheral blood mononuclear cells (PBMC) were stimulated with 10μg/ml LPS for 2.5 hrs or preincubated with a NO donor,S-nitroso-N-acetylpenicillamine (SNAP, 0.5mM) for 30 min, then stimulated with LPS in cell culture. Northern analysis and slot blots of mRNA for EGR-1 were performed using a 32P labeled cRNA probe for human EGR-1. In Northern blots of PBMC mRNA, EGR-1 expression increased from baseline when preterm, term and adult cells were stimulated with LPS. In slot blots of MN mRNA, EGR-1 expression again increased with LPS stimulation. With SNAP pretreatment, EGR-1 expression in response to LPS was blunted in adult MN whereas expression was increased in term and preterm cells. These results were confirmed with densitometry scanning. The neonatal samples had a clear increase in EGR-1 expression when pretreated with the NO donor when compared to stimulation with LPS alone. Nitric oxide modulation of the effect of LPS on EGR-1 expression is developmentally regulated. Understanding the developmental aspects of monocyte responses to the oxidant stress in various disease states will be important in the pursuit of efficacious therapies for the newborn at varying levels of maturation.