Increased soluble P-selectin has been described in atherosclerosis, but the mechanisms for this and its clinical significance are unknown. In an attempt to clarify these points we measured soluble P-selectin and von Willebrand factor, an endothelial cell marker, by ELISA in 116 patients who had survived a myocardial infarction and in 116 matched controls. Raised levels of both soluble P-selectin (median 272 ng/ml, range 55-850 ng/ml vs 190 ng/ml, range 40-395 ng/ml) and von Willebrand factor (mean +/- SD 128 +/- 37 IU/dl vs 100 +/- 33 IU/dl; both P < 0.001) failed to correlate (r = 0.12), and soluble P-selectin failed to correlate with any of the major risk factors for atherosclerosis. A four-year follow-up of 68 of these patients revealed that soluble P-selectin was higher in the 33 (48%) who had suffered an additional cardiovascular event (e.g. subsequent myocardial infarction, arterial surgery; median 350 ng/ml, range 275-460 ng/ml) compared with those free of an end-point (270 ng/ml, range 140-400 ng/ml, P = 0.0012). We conclude that increased soluble P-selectin is unrelated to the risk factors for atherosclerosis but is a new marker of disease progression in patients who have survived a myocardial infarction.