Recent data suggest that pentoxyfylline administration results in a significant reduction in serum TNF levels among OKT3-treated patients. However, the effect of pentoxyfylline on the clinical syndrome that ensues following OKT3 administration remains undefined. We evaluated 32 OKT3-treated renal transplant recipients to assess the impact of pentoxyfylline on OKT3 adverse reactions. The study population consisted of two groups: (i) a prospective group comprising 16 patients who received oral pentoxyfylline 600 mg 1-2 h prior to the first dose of OKT3 and then 600 mg every 8 h for 72 h, in addition to corticosteroids, acetaminophen and diphenhydramine, and (ii) an historical control group (n = 16) treated with corticosteroids, acetaminophen and diphenhydramine alone. All patients were evaluated for signs and symptoms consistent with the OKT3-induced cytokine-release syndrome. The incidence and clinical severity of OKT3-related adverse reactions were similar among the two groups. We conclude that oral administration of pentoxyfylline does not appear to affect the incidence or severity of OKT3-related adverse reactions.