Objective The role of A(1) adenosine receptors in preconditioning in humans is unknown. To establish whether bamiphylline, a selective antagonist of A(1) adenosine receptors, abolishes ischaemic preconditioning in man, 36 consecutive patients undergoing simple-vessel coronary angioplasty were randomized to receive intravenous infusion of bamiphylline (5 mg.kg(-1)) or placebo (0.9% NaCl) immediately prior to the procedure. Design The mean values (+/- 1 SD) of ST segment shifts on the surface and intracoronary electrocardiograms were measured at this end of the first and second balloon iaflations, both 2 min long. The severity of cardiac pain was obtained at the same time using a visual analogue scale. Results In bamiphylline-treated patients, the mean ST segment shift and the severity of cardiac pain during the second inflation were similar to those during the first inflation (14 +/- 15 vs 16 +/- 16 mm, ns and 31 +/- 28 vs 31 +/- 29, ns, respectively). Conversely, in placebo-treated patients both the mean ST segment shift and the severity of cardiac pain during the second inflation were significantly less than those during the first inflation (10 +/- 6 vs 17 +/- 17mm, P < 0.001 and 25 +/- 31 vs 39 +/- 31mm, P < 0.01, respectively). Thus, bamiphylline abolishes ischaemic preconditioning observed in man during repeated coronary balloon inflations. Conclusion These results suggest that, in this setting, ischaemic preconditioning is mediated, at least in part, by A(1) adenosine receptors.