We recently showed that collagen-induced platelet aggregation (PA) is enhanced by adrenaline ex vivo following cardiopulmonary bypass in man. Collagen-induced PA is impaired following bypass and this may contribute to postoperative blood loss, and aspirin treatment may further aggravate bleeding. To determine the influence of aspirin on the proaggregatory action of adrenaline following bypass, we assessed the effect of aspirin on collagen-induced PA before and after bypass, and following adrenaline infusion after bypass. Using optical aggregometry and hirudinised platelet rich plasma, in non-aspirin-treated controls (n=6), collagen (1.0 pg/ml) induced PA (median amplitude; cm) was maximal before bypass (13.7) and impaired at 10 min after bypass (11.5, P=0.03). PA was inhibited by aspirin (1 mM) before bypass (7.2 vs 13.7, P=0.03), and following bypass in aspirin-treated controls (3.3 vs 11.5,P=0.03). In aspirin-treated patients given adrenaline after bypass (n = 6), PA before adrenaline was impaired to a similar extent as in aspirin-treated controls (2.4 vs 3.3), but was enhanced following intravenous adrenaline infusion (0.55-1.1 nmol kg−1min−1) for 3-10 min (5.2 vs 2.4, P=0.03), with no change in controls at 20 min post-bypass (4.1 vs 3.3). This study indicates that at normocalcaemia, adrenaline enhanced collagen-induced PA in aspirin-treated patients, despite impairment of PA, but only at a high concentration of collagen. These findings indicate that aspirin-treatment may further impair collagen-induced PA following bypass, by limiting the proaggregatory effect of adrenaline.