The recent demonstration of aspirin's ability to prevent and reduce the severity of myocardial infarction has led to a marked increase in its use and to a need for information regarding the time-course of onset and offset of its antiplatelet effect. A study of healthy men was conducted to determine (1) the rapidity of onset of inhibition of platelet aggregation in response to adenosine diphosphate, and thromboxane A2 production after chewed enteric-coated aspirin (325 mg, n = 10); and (2) the duration of platelet inhibition after cessation of enteric-coated aspirin (325 mg) every other day for 14 days (n = 10). When chewed, enteric-coated aspirin greatly inhibited platelet aggregation response to adenosine diphosphate and thromboxane A2 production within 15 minutes. Complete recovery of platelet aggregation occurred in half of the subjects by day 3, and in 80% of the subjects by day 4; the platelet response was not affected by exercise. This study demonstrates a rapid onset of aspirin's antiplatelet effect and provides information relevant for optimal timing of initiation of aspirin for acute conditions such as myocardial infarction and unstable angina, and cessation of aspirin before surgery.