CONTEXT: Insulin can regulate immune cell function. Aging is associated with various degrees of insulin resistance together with reduced immune cell activity. OBJECTIVE: We investigated the hypothesis that blood monocytes and polymorphonuclear neutrophils (PMNs) are less responsive to the action of insulin in elderly subjects. DESIGN-INTERVENTION: We evaluated the effect of hyperinsulinemia (0.7 mU/kg(-1) fat-free mass per minute(-1)) on monocyte and PMN activity using a 4-h euglycemic clamp technique. PARTICIPANTS: Eight young (24 +/- 6 yr old) and nine elderly (69 +/- 4 yr old) healthy volunteers participated in the study. MAIN OUTCOME MEASURES: Monocyte and PMN receptor expression and density were measured using flow cytometric detection. PMN chemotaxis toward formyl-Met-Leu-Phe (fMLP) was evaluated using a two-compartment chamber. PMN and monocyte phagocytosis was determined by measuring the engulfment of opsonized particles. Microbicidal functions were determined based on the production of reactive oxygen species (ROS) and bactericidal protein by stimulated cells. RESULTS: The density of PMN and monocyte insulin receptors was not affected by age or insulin clamp treatment regardless of the age. Insulin was able to regulate the expression of receptors involved in PMN action in the young-adult group only. PMN chemotaxis was up-regulated by insulin in both groups. In contrast, although insulin stimulated phagocytosis and bactericidal activity in young-adult subjects, the ability of PMN to adapt to physiological hyperinsulinemia was blunted in the older group. The effect of insulin on monocyte bactericidal properties seemed to be limited, although a suppressive action on fMLP-induced ROS production was detected in young adults. CONCLUSIONS: We confirmed the presence of the insulin receptor on monocyte and PMN membranes. We revealed that insulin has a limited action on monocyte function. Insulin has a priming effect on the main PMN functions. Immune cell function adapted poorly to insulin infusion in the elderly subjects.