OBJECTIVE Agents which promote increased interstitial adenosine levels may be cardioprotective. The aim of this study was to evaluate the ability of 5-amino-1-beta-D- ribofuranosylimidazole-4-carboxamide (AICAr), an adenosine regulating agent, to limit infarct size when given before ischaemia, before coronary reperfusion, or postreperfusion in a rabbit preparation of ischaemia-reperfusion injury. METHODS The left coronary artery was occluded for 30 min and subsequently the ischaemic bed was reperfused for 180 min. Infarct size and risk zone size were delineated by tetrazolium staining and microsphere autoradiography, respectively. Four groups were studied: controls (n = 13), AICAr (2.5 mg.kg-1.min-1 intravenously for 5 min followed by 0.5 mg.kg-1.min-1 for 60 min) beginning either 5 min before coronary occlusion (n = 11), 5 min before coronary reperfusion (n = 11), or at 25 min coronary reperfusion (n = 10). Lignocaine was not given in these experiments. RESULTS Infarct size, normalised to risk zone, was significantly reduced with AICAr given 5 min before coronary reperfusion, at 35.0(SEM 4.4)% v 51.8(3.9)% in controls; p = 0.03. Cardioprotection was not observed when AICAr was given either 5 min before coronary occlusion [44.2(4.8)%] or 25 min postreperfusion [45.9(3.2)%]. CONCLUSIONS These findings support the hypothesis that adenosine regulating agents, such as AICAr, can modulate infarct size in this rabbit preparation of ischaemia-reperfusion injury.