The aim of this study was to evaluate the role of endogenous histamine in the regulation of reactive hyperaemia (RH) and coronary autoregulation in isolated rat hearts. The basal release of cardiac histamine (perfusion pressure 60 cm H2O) amounted to 100-200 pmol/min/g wL During the first 15 s following 30 s of coronary occlusion, the release of histamine increased about three times and returned to basal levels after approximately 90 s, paralleling the changes of coronary flow (CF). Blockade of Hi-receptors increased basal CF by 23±2 %, significantly reduced blood flow debt and prolonged the duration of RH. Blockade of H2- and H3-receptors produced a significant decline of CF, decreased RH flow and diminished RH by 40±3 %. Blockade of all three classes of histamine receptors indicated that endogenous histamine exerts predominantly vasodilatory effects (mediated by H2- and H3-receptors) on coronary circulation. Histamine-induced vasodilation appears to be NO-dependenL Changes of coronary perfusion pressure from 20 to 120 cm H2O were accompanied by an almost linear decrease of histamine release from about 200 to 40-50 pmol/min/g wL Blockade of histamine receptors decreased, while L-NAME significantly widened the autoregulatory range of the isolated rat heart, reduced CF and release of NO, but reversed the pattern of histamine release leaving the autoregulatory range unaltered, which indicate that endogenous histamine does not play a role in the regulation of coronary autoregulation.