Because cardiac complications after myocardial infarction are more frequent in diabetics, we tested whether experimentally-induced diabetes may increase ischaemic myocardial injury in 23 rabbits. Diabetes was induced in randomized rabbits with the alloxan method. After 2 months, diabetic rabbits underwent a 30-min coronary occlusion followed by 3-h reperfusion and were compared with controls. Collateral flow was measured by the radioactive microsphere technique and infarct size by tetrazolium staining. Infarct size represented 28.6+/-4% of area-at-risk in controls and 16.5+/-3% in diabetics (P<0.05). Collateral flow (0.06+/-0.03 ml/min/g in controls and 0.014+/-0.004 ml/min/g in diabetics) and area-at-risk (50.2+/-4.2% of left ventricle in controls and 53.9+/-5. 4% in diabetics) were similar in both groups. There was a significant positive correlation between area-at-risk and infarct size in both groups (r=0.60 and 0.70, respectively) and for a given area-at-risk, diabetic rabbits developed smaller myocardial infarction than controls (covariance analysis, P<0.01). In additional experiments, hyperglycemia induced by intravenous glucose infusion in non-diabetic rabbits did not protect the ischaemic myocardium (infarct size: 37.9+/-12.5%). In conclusion, diabetes in the rabbit induces a chronic and metabolic form of preconditioning. Further studies are needed to explore the mechanism and time course of this protection.