Cytokine release and clinical side effects resulting from the use of OKT3 and BMA 031 monoclonal antibodies in the treatment of kidney graft recipients were evaluated and compared. The rise observed in serum levels of interferon gamma. TNF alpha, and IL-8 was similar after administration of either monoclonal antibody. Furthermore, both OKT3 and BMA 031 resulted in rapid disappearance not only of virtually all T cells, but also of substantial percentages of all major leukocyte populations from the circulation; this effect is probably due to cytokine release activating endothelial cells and thereby causing extravasation even of leukocytes not specifically recognized by the administered antibodies. Evidence has thus been obtained that BMA 031 is as potent as OKT3 in inducing unequivocal signs of T cell activation in vivo. However, while OKT3 therapy was accompanied by adverse side effects in our study as in previous ones, we saw no such reactions in any of the patients receiving BMA 031. This contrast might be due to different mechanisms of leukocyte activation possibly inducing other mediators in the case of OKT3, which then, in combination with the cytokines, could generate treatment-associated morbidity.