In addition to its ability to improve microcirculation, pentoxifylline also has anti-tumor necrosis factor-alpha (TNF) actions which have prompted investigations into its potential efficacy in disease states involving elevated TNF levels. One such disease entity is AIDS where aberrant TNF seems to mediate axonal degeneration within thecentral nervous system. To this end, we have previously established a rabbit model of TNF-mediated axonal degeneration, and demonstrated that pentoxifylline attenuates this effect. Unfortunately, there has been to date only one limited report on the pharmacokinetics of pentoxifylline in rabbits. Therefore, the present report evaluates plasma levels of pentoxifylline and two of its primary metabolites through high-performance liquid chromatography after both the oral and subcutaneous administration of pentoxifylline. Our results indicate that in rabbits there is a very rapid absorption and metabolism of pentoxifylline after either oral or subcutaneous administration. In comparison with the mouse, the rabbit seems to absorb and metabolize pentoxifylline slower. In contrast to man, the rabbit had lower metabolite plasma levels than the parent drug itself.