The aim of the present study was to evaluate platelet responsiveness in rats following E.coli endotoxin administration. Injection of E.coli to rats caused a reduction in ADP-induced pulmonary 111In labelled platelet accumulation four hours later. Similarly, when platelet aggregation was evaluated on PRP obtained from rats four hours after endotoxin administration, we found that platelet response to both ADP and collagen was significantly reduced. When platelets obtained from endotoxemic rats were suspended in normal plasma, the aggregating response to ADP and collagen was not different from that obtained with control platelets. Similarly, platelets from control rats suspended in plasma from endotoxemic rats showed hyporesponsiveness to ADP and collagen. There was no difference in the aggregatory response to collagen or to thrombin of washed platelet suspension (WPS) obtained from endotoxemic and normal rats. In conclusion, by using an in vivo minimally invasive technique and an ex vivo platelet aggregation test we demonstrate that during endotoxemia platelet are functionally unaltered and the platelet hyporesponsiveness is only observed in presence of plasma.