The influence of pentoxifylline on normal and diseased neutrophil function has been studied in vitro. In high concentrations pentoxifylline stimulated human neutrophil chemotaxis toward both bacterial oligopeptides and complement components. Pentoxifylline was also shown in vitro to restore the normal chemotactic capacity of neutrophils from patients with known functional defects, i.e. myelodysplastic syndromes, lazy leucocyte syndrome, juvenile parodontitis, hyper-IgE-syndrome and liver cirrhosis. Pentoxifylline was also shown to strongly inhibit the release of primary and secondary granule release of granulocytes. Moreover, pentoxifylline inhibits both basal and stimulated neutrophil adhesion to both aortic and pulmonary artery calf endothelium. The mechanism whereby pentoxifylline exerts this action is not adequately understood. While our results partially imply interference of pentoxifylline with neutrophil cyclic AMP and/or prostaglandin metabolism, down-regulation of neutrophil functional antigen (e.g. CD11, CD18) expression seems to play a key role in the observed drug effects. Finally, these results indicate that pentoxifylline may be useful in the treatment of granulocyte mediated diseases and symptoms.