We studied contractile effects in isolated electrically driven (1Hz) atrial preparations from patients undergoing cardiac bypass surgery. Adensine triphosphate (ATP) concentration-dependently (10, 30, 100 µM) rapidly decreased force of contraction (negative inotropic effect, NIE) and thereafter more slowly increased force of contraction, the maximum positive inotropic effect (PIE) at 100 µM ATP amounted to 152 % of pre-drug value (n=9), was stable and could be washed out fast and completely. The PIE did not affect time parameters of contraction (time to peak tension and time of relaxation). Moreover, a similar NIE and PIE were noted with ATPS (100 µM). In contrast 2-methyl-thio-ATP did not exert a NIE but only a PIE. In a second set of experiments, preparations were first incubated for 30 min with purinoreceptor-antagonists and in their continuous presence, 100 µM ATP was applied. However, the PIE as well as the NIE of ATP could neither be blocked with suramin (100 µM and 500 µM) nor PPADS (50 µM) nor reactive blue 2 (30, 100, 500 µM), which are known blocker for subtypes of P2-receptors, or DPCPX (1 and 10 µM), a subtype (A₁-adenosine) P1-receptor blocker. Likewise the inhibitor of PLC activity U73122 and the inhibitor of adenylate cyclase activity SQ22563 (10 µM, each) failed to affect the NIE and the PIE of ATP. We tentatively suggest that the PIE of ATP might be mediated via P2X₄-like receptors. In summary, we describe a novel biphasic effect of ATP on force contraction in the isolated human atrium. It is conceivable that ATP plays a physiological role in the human heart, for instance after cardiac injury in order to sustain contractility.