Cecal ligation and puncture (CLP) were performed in rats. After 4 hr (early sepsis) and 16 hr (late sepsis), platelet morphology and function were studied. At 16 hr, platelet counts for the CLP group were significantly lower than for the sham-operated control group. Low maximum aggregation rates (MAR) and decreased platelet counts were elicited in platelet-rich plasma with 4 M ADP and 2 micrograms/ml collagen. However, with platelet counts equalized, MAR for the CLP group increased significantly, especially after 16 hr. The platelet-large cell rate and platelet distribution width decreased temporarily at 4 hr, then rose significantly at 16 hr. No significant changes were observed in the mean platelet volume after 4 hr, but there were significant increases after 16 hr. Total adenine nucleotide (TAN) levels within the platelets rose significantly in the CLP group, suggesting the appearance during the late sepsis of large, heavy platelets or adenine nucleotide-rich platelets. The platelet adenylate pool was divided into granular and cytoplasmic fractions, respectively characterized by ADP and ATP increases. However, no septicemia-related differences were noted in the degree of binding between goat antirat fibrinogen and platelet surface glycoprotein IIb/IIIa complex. Internal environment changes in the platelets indicated that during septicemia hyperfunctional or hypersensitive platelets with a latent capacity for active aggregation and release appeared in the circulation. Hypercoagulability in septicemia involves activation of coagulation factors, stimulation of the coagulation cascade, volume changes accompanying increased platelet TAN content, and changes in AN distribution in the two pools. These findings significantly increase our understanding of the transition from the prethrombotic state to thrombosis in septicemia.