1. In rats treated with S-adenosyl-L-methionine (SAMe), platelet aggregation in whole blood was inhibited by 50-57% with respect to control values. 2. In whole blood, SAMe also inhibited platelet aggregation, particularly when aggregation was induced with collagen (maximum inhibition 78.6 +/- 5.8% with 10(-5) M SAMe). 3. The antiaggregant response was seen with SAMe in the range of concentrations from 10(-7) to 10(-5) M, whereas concentrations in the range from 10(-4) to 10(-3) M had a progressively weaker effect. 4. Both red blood cells and leukocytes enhanced the antiaggregant effect of SAMe, as did simultaneous incubation with L-arginine. 5. The intraplatelet concentration of glutathione also was increased by SAMe.