In vitro deformability of red blood cells from SS-genotype patients in vasoocclusive crisis of sickle cell disease was significantly improved by the in vitro addition of the xanthine derivative pentoxifylline (Trental). Monkeys transfused with discarded sickle cell crisis blood showed aggregation of red cells and platelets on metal screens inserted into arterio-venous anastomoses. This phenomenon could be prevented by pretreatment of the animals with 24 mg/kg of pentoxifylline. The possible mechanisms of action are discussed.