Circulating thromboxane (TX) is elevated following endotoxin, and platelets become hyperaggregable. Thromboxane synthesis was therefore studied in platelets during endotoxemia. Rabbit blood and platelets were taken at 0, 60 and 120 min after start of E. coli endotoxin infusion (1.10 microgram/kg min, i.v.). Blood incubation with arachidonic acid (AA, 10(-4) M) generated TXA2, which was measured using a superfused rabbit aorta bioassay. Washed platelets were stimulated with 1-14C AA (0.1 microCi) to generate radiolabeled TXB2, which was isolated by TLC and quantitated by scintillation spectrometry. Control (0 time) platelet count was 488 +/- 10(3)/mm3. In the test group, platelet counts fell to 65% of control at 60 min and to 52% at 120 min, while TXA2 generation was 95% (60 min) and 94% (120 min) of control. In contrast a serial dilution of untreated platelets yielded a progressive decline in thromboxane generation. In endotoxemic platelets, the conversion of 1-14C AA to TXB2 (percent/10(9) platelets) was increased at 120 min (0 min, 34.7; 120 min, 40.0: P less than 0.05). Endotoxemic platelets generated greater amounts of thromboxane than did normal platelets, and this condition may account for platelet hyperaggregability in shock.