We treated red cells and platelet sepatatelyin vitrowith aspirin or indomethacin to inhibit platelet function. The excess of drug was removed by profuse washing prior to blood reconstitution. We examined the influence of such treatments on platelet interaction with vascular subendothelium employing a perfusion system. Treatment of red cells or platelets with aspirin showed a similar pattern of platelet deposition onto subendothelium. However, platelet adhesion was significantly increased in treated red cells (21.7±2.7% vs 13.7±1.9% in controls;P<0.05) whereas thrombus was significantly decreased in treated platelets (6.2±1.62% vs 13.8±1.7% in controls;P<0.05). Treatment of red cells or platelets with indomethacin strongly inhibited platelet interaction. Thrombus and covered surface were decreased in experiments with treated red cells (2.3±0.73% and 14.9±2.3%, respectively;P<0.05). Adhesion, thrombus and covered surface were decreased in experiments with treated platelets (4.3±0.7%, 2.3±0.9%, 9.2±1.5%, respectively;P<0.05). Platelet aggregation experiments performed with aspirin-treated red cells showed a progressive inhibition of platelet function. Testing levels of drug in plasma samples from the perfusates showed that levels of drug were very similar to those obtained if treated red blood cells were not washed after treatment. All these results suggest that red cells retained some quantities of drug. Our data highlight the potential effect of red cells interfering with platelet function inhibitors.