OBJECTIVE The aims were (1) to determine whether ischaemic and hypoxic preconditioning enhance recovery of left ventricular function after global ischaemia in the rat, and (2) to evaluate the effects of selective adenosine A1 receptor antagonists on ischaemic and hypoxic preconditioning. METHODS Isolated rat hearts, perfused at constant pressure, were subjected to 30 min ischaemia and 30 min reperfusion. Control hearts were compared to hearts preconditioned with 5 min ischaemia in the presence or absence of the adenosine A1 antagonist A1433U (10 microM), and hearts preconditioned with 5 min hypoxia in the presence or absence of the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 5 microM). Recovery of left ventricular function was assessed by percent recovery of preischaemic rate-pressure product. RESULTS Control hearts recovered 64(SEM 4)% of preischaemic rate-pressure product after 30 min reperfusion, whereas ischaemic and hypoxic preconditioned hearts recovered 86(3)% and 94(5)%, respectively (p < 0.05 v control). Despite enhanced recovery of postischaemic ventricular function, ischaemic and hypoxic preconditioning reduced the time to onset of ischaemic contracture from a control value of 12.6(0.6) min to 9.3(0.7) and 9.0(0.6) min, respectively (p < 0.05). Neither adenosine receptor antagonist blocked preconditioning. Ischaemic preconditioned hearts recovered 80(5)% of preischaemic function in the presence of A1433U, and hypoxic preconditioned hearts in the presence of DPCPX recovered 85(4)%. CONCLUSIONS Ischaemic and hypoxic preconditioning enhance recovery of function following global ischaemia in the rat. The observations that adenosine receptor antagonists do not block the salutary effects of ischaemic or hypoxic preconditioning suggest that adenosine is not the sole mediator of preconditioning.