Experimental data derived from animal models suggest that the endogenous nucleoside adenosine has important cardioprotective properties. The potent vasodilator effects of adenosine may contribute to this cardioprotection as ischaemia-induced release of endogenous adenosine has been suggested to adjust local blood flow to the metabolic demands of the tissue. Interestingly, the vascular effects of adenosine appeared to be impaired in animal models for diabetes mellitus. This observation may be of importance with respect to the increased cardiovascular mortality in diabetes. Therefore, the authors investigated the in vivo vasodilator effects of adenosine in insulin-dependent diabetic patients. In 12 uncomplicated insulin-dependent male diabetic patients and 12 healthy male age-matched subjects, the brachial artery was cannulated for infusion of adenosine (0 center dot 15, 0 center dot 5, 5, 15 and 50 mu g 100(-1) mL min-1) and for measurement of mean arterial pressure (MAP). Forearm blood flow (FBF) was measured by venous occlusion mercury-in-silastic strain gauge plethysmography. Maximal vasodilatation was assessed by standardized post occlusive reactive hyperaemia (PORH). Baseline forearm blood flow was 2 center dot 7 +/- 0 center dot 4 and 1 center dot 8 +/- 0 center dot 2 mL 100(-1) mL min-1 for the diabetic patients and control group respectively. In the diabetic patients, adenosine infusion raised forearm blood flow to 2 center dot 4 +/- 0 center dot 4, 2 center dot 6 +/- 0 center dot 4, 4 center dot 4 +/- 0 center dot 7, 6 center dot 3 +/- 1 center dot 0, 9 center dot 8 +/- 1 center dot 5 and 14 center dot 2 +/- 2 center dot mL 100(-1) mL min-1 for the respective dosages. In the control group these values were 1 center dot 7 +/- 0 center dot 2, 1 center dot 9 +/- 0 center dot 3, 3 center dot 2 +/- 0 center dot 8, 6 center dot 0 +/- 1 center dot 2, 10 center dot 9 +/- 2 center dot 1 and 17 center dot +/- 3 center dot 4 mL 100(-1) mL min-1 respectively (P > 0 center dot 1 for between group comparison). Forearm blood flow at the contralateral side was not significantly affected by the placebo and adenosine infusions. Similar results were obtained when results were expressed as changes in forearm vascular resistance or forearm blood flow ration (FBF infused arm/FBF control arm). Maximal vasodilatation did not differ between the two groups. The authors conclude that the forearm vasodilator response to adenosine is preserved in uncomplicated insulin-dependent diabetic patients. This observation argues against a primary role of a reduced adenosine responsiveness in the cardiovascular sequelae of diabetes.