The possible release of histamine into the coronary circulation during reperfusion of the cold, cardioplegic heart was investigated during open heart surgery in 13 patients (cardioplegic arrest 54 (35-120 min) (median (range)), cardiopulmonary bypass (CPB) 96 (65-360) min. Samples were drawn concomitantly from coronary sinus and arterial blood before cardioplegia and during myocardial reperfusion for measurement of histamine (radioenzymatic method). Additional arterial samples were drawn pre-, per- and postoperatively. CPB induced a sustained increase in arterial histamine (from 4.02 +/- 2.71 nmol/l preoperatively (mean +/- SD) to maximum 16.31 +/- 7.12 nmol/l, p < 0.009). Immediately before cardioplegia histamine levels were higher in arterial than coronary sinus blood (9.24 +/- 4.85 versus 4.04 +/- 2.07 nmol/l, p < 0.002). During myocardial reperfusion coronary sinus histamine increased to levels similar to that of arterial blood. In conclusion, histamine is released during CPB. Before cardioplegic arrest, there is a net uptake of histamine by the heart, which is abolished during reperfusion, possibly due to increased cardiac release of histamine.