To assess the relationship between the direction of ST segment response to transient coronary occlusion and collateral function, we studied 25 patients with diagnostic ST segment changes during transient occlusion of the proximal left anterior descending artery (LAD). Electrocardiographic leads I, II, V2, and V5; left ventricular filling, aortic, and distal coronary pressures; and great cardiac vein flow were measured during percutaneous transluminal coronary angioplasty (PTCA) of the LAD. During a 1 min LAD balloon occlusion, 16 patients had reversible ST elevation (group I) and nine patients had ST depression (group II). The ST responses in individual patients were consistent during repeated occlusions, and ST depression never preceded ST elevation. Angiography before PTCA showed less severe LAD stenosis in group I (69 ± 15%) than in group 11 (88 ± 10%; p < .01) and collateral filling of the LAD in no group I patient but in six of nine patients in group II (p < .00 1). During LAD occlusion, determinants of myocardial oxygen demand (left ventricular filling pressure, aortic pressure, heart rate, and double product) were similar in both groups. Group I patients, however, had lower distal coronary pressure (25 ± 8 vs 41 ± 16 mm Hg) and residual great cardiac vein flow (33 + 14 vs 51 ± 22 ml/min) and higher coronary collateral resistance (3.1 ± 2.1 vs 1.5 ± 0.8 mm Hg/ml/min) than group II patients (all p < .05). In patients with ST elevation during LAD occlusion, stenosis before PTCA was less severe, visible collaterals were not present, and hemodynamic variables during LAD occlusion reflected poorer collateral function. Collateral function is an important determinant of the direction of ST segment response to ischemia during acute coronary occlusion.