The Baumgartner perfusion technique was used as an experimental model to study the combined influence of red cell (RBC) and platelet counts on the interaction of platelets with the subendothelium. At normal hematocrit and a platelet count of 100,000 per microliter, platelet adhesion and platelet aggregate (PAG) formation on subendothelium were statistically decreased. At lower platelet counts (50,000/microliter), there was an even more marked reduction in the formation of PAGs. The critical role of RBCs was demonstrated in experiments at low hematocrit; the formation of PAGs was impaired in perfusions at 20 percent hematocrit at any platelet count tested. Platelet deposition on subendothelium was almost absent at 50,000 platelets per microliter, suggesting a negative synergistic effect for the association of low hematocrit (20%) with a low platelet count. Perfusion experiments carried out with nonanticoagulated blood drawn directly from anemic patients with mild thrombocytopenia (43,000-58,000 platelets/microliter) before and after RBC transfusion were in agreement with previous experiments that indicated that normalization of both platelet count and hematocrit is required to achieve optimum hemostasis. Our data give experimental support for the transfusional management of patients with anemia and thrombocytopenia.