Pentoxifylline is a methylxanthine derivative used to increase blood flow in peripheral atherosclerosis. Pentoxifylline is known to increase whole blood filtration rate, and recent evidence suggests that pentoxifylline increases the filtration rate of polymorphonuclear leukocytes (PMNs). The purpose of this study was to directly observe and quantitate the effect of pentoxifylline on the flow of individual PMNs into a model capillary. Short-term incubation of human PMNs with 10 mM pentoxifylline inhibited cell activation, as judged by a significant reduction in the number of neutrophils forming pseudopods. Furthermore, incubation of PMNs from 6 healthy men with 0.1, 1.0 and 10 mM pentoxifylline significantly decreased the time required for individual cells to be aspirated into a 4 microns pipet under constant pressure by 16 +/- 5%, 21 +/- 7%, and 41 +/- 8%, respectively (mean +/- SEM, p less than or equal to 0.05), compared with control. These experiments are the first direct demonstration of increased deformability in neutrophils treated with pentoxifylline. The results are consistent with the hypothesis that the beneficial effect of pentoxifylline on microvascular perfusion is partly due to an inhibition of PMN stiffness and activation.