The contribution of relative lead strengths to ST depression during exercise was evaluated in 334 patients who had both a treadmill stress test and an angiogram. Patients were referred for exercise testing for the evaluation of suspected or known coronary artery disease. This was accomplished by comparing the magnitude of ST-segment depression to a constructed ST/R ratio. Using a cutoff of 0.1 for the ST/R ratio, the data were compared to the sensitivity and specificity of the 1 mm criteria for ST depression. There was only a slight increase in sensitivity (59% vs 63%) and specificity (60% vs 78%) for the ST/R ratio in comparison to the standard ST depression. However, when these two criteria were reevaluated for patients with less than or equal to 10.0 mm of R wave amplitude, the 0.1 ST/R ratio had a small decrease in specificity (94% vs 80%) when compared to 1 mm of ST depression and a marked increase in sensitivity with 31% for the standard ST depression and 82% using the ST/R ratio. In those with an R wave greater than 20 mm, 1 mm of ST depression was much more sensitive than the ST/HR ratio (95% vs 59%), but the ratio was more specific than the conventional ST depression (78% vs 59%). It is concluded that ST depression should be corrected for R wave amplitude in patients with R waves less than 10 mm and over 20 mm.