Immunomodulating agents are being investigated for treatment of infection in newborn infants where morbidity and mortality remain high despite the continued development of new antibiotics. We studied the effect of the methylxanthine pentoxifylline on polymorphonuclear leukocyte (PMN) chemotaxis, F-actin content, and phagocytic activity as measured by nitroblue tetrazolium reduction and H2O2production in neonates and adults to determine whether pentoxifylline might be useful in augmenting PMN function. The drug was found to have a dose-dependent effect on both neonatal and adult PMN function with enhancement at lower concentrations and suppression at higher concentrations. PMN chemotaxis increased 42% (p < 0.01) in neonates and 16% (p< 0.05) in adults at 100 μg/mL of pentoxifylline and it decreased 4 and 25%, respectively, at 4000 μg/mL. PMN nitroblue tetrazolium reduction increased by 34% in neonates and 23% (p< 0.05) in adults at 100 μg/mL of pentoxifylline and decreased by 52 (p< 0.01) and 74% (p< 0.01), respectively, at 2000 μg/mL. Similar dose-dependent responses were noted with F-actin content and H2O2production. These and other observations support the hypothesis that pentoxifylline has a broad range of effects on PMN but that a primary effect is alteration of PMN deformability. Pentoxifylline has potential clinical use as an immunomodulator in augmenting impaired PMN function in neonates and other immunocompromised hosts or in suppressing excessive PMN activity in certain disease processes. (Pediatr Res29:123–127, 1991)