The aim of this study was to attenuate side effects of OKT3 by variation of the time interval between administration of corticosteroids and OKT3 in renal allograft recipients. In view of a maximal lymphocytopenia at six hours following MPNS, we postulated a greater preventive action on side effects from administration of methylprednisolone (MPNS) at six hours preceding the first dose of OKT3 compared to administration immediately before. Two groups of renal transplant patients treated for acute rejection with 5 mg OKT3 were studied. Ten patients received 500 mg MPNS six hours and ten patients one hour before administration of OKT3. We measured clinical side effects, body temperature, TNF and IL-6. There were no differences between the two groups regarding clinical side effects and peak body temperatures. However, MPNS administered six hours before administration of OKT3 diminished TNF release; MPNS one hour before decreased IL-6 release. We studied an additional group of six patients receiving 250 mg MPNS six hours before, followed by 250 mg one hour before OKT3. This group experienced significantly less side effects and lower body temperature. In addition, IL-6 levels were significantly decreased. We conclude that two times 250 mg MPNS administered six hours and one hour before the first administration of OKT3 effectively attenuates adverse reactions following administration of OKT3.