P-selectin is an important marker of platelet activation and may be up-regulated in patients with congestive heart failure (CHF). We sought to prospectively compare simultaneously determined platelet and soluble P-selectin in patients with CHF and in healthy controls. Matched soluble levels by enzyme-linked immmunosorbent assay, and platelet-bound expression by whole blood flow cytometry of P-selectin were measured in 22 patients with CHF and compared with 14 healthy controls. Twelve patients were aspirin free and 10 patients were taking aspirin (81 to 500 mg/day). Patients with CHF had significantly elevated soluble P-selectin (186.6 +/- 82.7 ng/ml, p = 0.017) and more than twofold increased expression of platelet-bound P-selectin (9.58 +/- 7.16% of positive platelets, p = 0.021) compared with the P-selectin profile (102.6 +/- 29.0 ng/ml of plasma, and 4.06 +/- 1.21% of positive platelets, respectively) in controls. Aspirin therapy did not affect the P-selectin profile in patients with CHF. Despite antecedent aspirin therapy and interindividual variability of the P-selectin profile, soluble and platelet P-selectin were elevated in most patients with severe CHF, suggesting persistent platelet activation.