The growing knowledge on the pathophysiological role of cytokines in acute and chronic inflammatory processes stimulated efforts to control their synthesis and action pharmacologically in clinical situations. Recently, in our institute evidence was raised that pentoxifylline (POF) is able to suppress the synthesis of tumor necrosis factor-alpha (TNF) in cell cultures, in vivo, and to protect experimental animals against endotoxin shock. Studies in human experimental endotoxemia showed that pentoxifylline decreased circulating TNF without affecting endogenous formation of interleukins. The potency of this drug to interfere with TNF synthesis could also be demonstrated in cases of acute and chronic cytokine release syndromes such as OKT3 first-dose reaction and severe pulmonary tuberculosis, respectively. We suggest that POF may improve therapeutic strategies in various diseases in which TNF was identified as a causative pathophysiological factor.