Platelet-activating factor (PAF) is a potent phospholipid mediator which has been implicated in the pathophysiology and complications of diverse clinical illness such as myocardial infarction and shock. 10 normal males, 13 presenting with acute myocardial infarction and 13 with clinical sepsis were studied. In myocardial infarction, plasma PAF, platelet PAF receptor number and platelet-associated PAF were not significantly different from normal. In clinical sepsis, plasma PAF was not different and platelet-associated PAF was slightly, but not significantly, higher. Similarly, in this group, the production of PAF from resting and stimulated neutrophils was not different from normal. Despite significant experimental evidence from animal studies for the involvement of PAF in cardiovascular disorders, this clinical study provides little direct evidence to support this view. Our results suggest that PAF is maintained at a relatively constant circulating level, a consequence of metabolic regulation and a high avidity for platelets and neutrophils.