Determinants of the ST-segment response to exercise can be mathematically modeled by solid-angle theory, and heart rate adjustment of the magnitude of exercise-induced ST-segment depression can remodel the solid-angle relationship to provide a theoretic and practical basis for application of heart rate-adjusted indexes of ST depression in exercise electrocardiography. Solid-angle theory indicates that the magnitude of ST depression recorded at a surface electrode (ε) can be described as the product of spatial and nonspatial determinants: ε = (Ώ4π) · (ΔV m) · K (equation 1), where Ω is the solid angle subtending the boundary of the ischemic territory, ΔV m is the difference in transmembrane voltage between the ischemic and adjacent nonischemic regions, and K is a term correcting for differences in intracellular and extracellular conductivity and changes in end-plate conductance. As a consequence, the magnitude of ST depression recorded by a surface electrode will be proportional both to the area of ischemic territory subtended by the recording electrode, which reflects the solid angle, and to the local transmembrane potential difference, which in turn reflects the electric consequences of the metabolic severity of ischemia at the level of the myocardial cell. It follows from equation 1 that the amplitude of ST depression can accurately reflect the area of ischemic boundary only when the severity of ischemia is constant or otherwise controlled, and differences in ST depression will only reflect varying areas of underlying ischemia when similar severity of ischemia is present. During exercise the severity of ischemia is directly proportional to changes in myocardial oxygen demand and coronary blood flow, which in turn are directly related to increasing heart rate (ΔHR). Because the change in transmembrane voltage across the ischemic boundary is linearly proportional to ΔHR, ΔV mΔHR remains constant as ischemia develops. Dividing the solid-angle relationship in equation 1 by ΔHR and making the appropriate substitution for a constant ΔV mΔHR then indicates that εΔ HR = (Ώ4π) · (c · K) [equation 2], where c is the new constant. Under conditions where changes in conductance are proportional or small, this simplified relationship reduces to ΔSTΔHR= c′ · Ω [equation 3], where ΔST reflects the magnitude of ST depression recorded by the surface electrode, ΔHR the change in heart rate during developing ischemia, and c′ the resulting empiric constant. In effect, these equations reveal that during ischemia the ratio of ΔST to ΔHR should be directly proportional to the area of ischemic boundary, but not to the metabolic effects of ischemic severity on transmembrane potential differences across the ischemic boundary. These relations provide a theoretic model for the practical application of HR adjustment of ST depression to the evaluation of coronary disease.