Circulating platelet microthrombi were evaluated during the acute and convalescent phases of illness in 44 patients admitted to the hospital for chest pain. Similar studies were performed in 10 healthy volunteers and 6 patients with infection. Circulating platelet microthrombi were significantly increased during the acute phase in 22 patients with transmural myocardial infarction compared with values in the other 22 patients without myocardial infarction, the healthy volunteers and the patients with infection alone. This increase in circulating platelet microthrombi declined to normal levels by the 7th hospital day in all but two patients who had evidence of extension of myocardial infarction and died. In contrast, circulating platelet microthrombi were similar in acute and convalescent phases of patients with chest pain but without myocardial infarction and were comparable with values in healthy volunteers. This study suggests that increased circulating platelet microthrombi may be related to tissue necrosis associated with transmural myocardial infarction.