We previously demonstrated that pentoxifylline stimulated leukocyte migration in vitro and leukocyte accumulation in vivo and protects neonatal mice from experimentally induced Staphylococcus aureus infections. In the present studies we have investigated pentoxifylline's effect on human leukocyte function in vitro. In these studies we demonstrate that pentoxifylline at low concentrations (ie, 0.01 and 0.1 mg/ml) stimulates both leukocyte migration and microbicidal activity in vitro. Alternatively, low concentrations (0.001 to 0.1 mg/ml) of pentoxifylline had no significant effect on the binding uptake of S. aureus by leukocytes, nor did it enhance phagocytic degranulation. At extremely low concentrations (0.001 mg/ml), pentoxifylline enhanced oxygen metabolism by human leukocytes, as reflected by increased H2O2 production and chemiluminescence (CL). At higher concentrations (ie, 0.1 to 1 mg/ml), pentoxifylline consistently suppressed these leukocyte functions in vitro. Thus, this study supports the following hypothesis: 1) the in vivo effects of pentoxifylline may involve a direct effect on both leukocyte mobilization and microbicidal activity, and 2) the enhanced microbicidal activity induced by pentoxifylline may be a result of enhanced leukocyte oxygen metabolism. In summary, pentoxifylline appears to be an interesting immunomodulator (ie, immunoenhancement and immunosuppression) of leukocyte function in vitro, but additional studies will be required before the efficacy of pentoxifylline in man can be determined.