The effects of glucose-insulin-potassium (GIK) on cardiac metabolism have been studied previously in non-diabetic patients after cardiac surgery. Although patients with diabetes mellitus can be expected to benefit most from such treatment, the impact of GIK in diabetic patients undergoing cardiac surgery remains unexplored. Therefore the present study investigates the effects of high-dose GIK on myocardial substrate utilization after coronary surgery in patients with Type II diabetes. A total of 20 patients with Type II diabetes undergoing elective coronary surgery were randomly allocated to either post-operative high-dose GIK or standard post-operative care, including insulin infusion if necessary to keep blood glucose below 10 mmol/l. Myocardial substrate utilization was studied using the coronary sinus catheter technique. Haemodynamic state was assessed with the aid of Swan-Ganz catheters. High-dose GIK caused a shift towards carbohydrate utilization, with significant lactate uptake throughout the study period and significant uptake of glucose after 4 h. Arterial levels of non-esterified fatty acids and beta-hydroxybutyric acid decreased, and after 1 h no significant uptake of these substrates was found. Increases in the cardiac index and stroke volume index were found in patients treated with high-dose GIK. A decrease in systemic vascular resistance was found both in the control group and in the high-dose GIK group. We conclude that high-dose GIK can be used in diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of non-esterified fatty acids and beta-hydroxybutyric acid. This could have implications for treatment of the diabetic heart in association with surgery and ischaemia.