OBJECTIVE The aim of the study was to determine whether moderate reduction in regional myocardial blood flow is related to epicardial ST segment depression and to the changes in grade and extent induced in this variable by antianginal drugs. METHODS Blood flow through the anterior descending coronary artery was reduced to 25-30% of control in open chest dogs, using a cuff flow meter as a monitor, and glyceryl trinitrate, propranolol and nifedipine were infused 60 min later. Regional left ventricular blood flow was measured with 15 mu radioactive microspheres and electrocardiograms were recorded from the epicardial surface of the anterior left ventricular wall before and after administration of the drugs. METHODS 20 adult male greyhounds were used, weighing 19-24 kg. RESULTS Under control conditions there was a poor correlation between ST segment depression and regional flow. Neither glyceryl trinitrate nor nifedipine had any significant effect on ST segment depression in sites overlying zones with a flow range of 80-105% of normal flow. On the other hand, glyceryl trinitrate, but not nifedipine, decreased ST segment depression in sites overlying the central ischaemic zone (35-80% of control posterior wall flow). With propranolol, mean ST depression was decreased significantly in sites overlying the central ischaemic zone (35-80% of control flow), but not in sites overlying zones with flows ranging from 80-105% of normal. Propranolol reduced blood flow to all zones. CONCLUSIONS Epicardial ST segment depression is unreliable for the quantitative exploration of the grade and extent of myocardial ischaemia.