We examined the prognostic significance of an obstructive lesion in the proximal left anterior descending (LAD) coronary artery. Five-year or longer follow-up data were examined from 311 patients with greater than 70% obstruction of the LAD treated without surgery. Mortality was compared in subsets with lesions proximal to and distal to the first septal perforating artery. Survival curves were worse in patients with proximal than with distal LAD disease (p less than 0.05); lesion location remained a significant determinant of survival when ejection fraction, age, and sex were controlled using a Cox regression model. However, when patient subsets were examined, survival with proximal LAD disease was worse than with distal obstruction only in the presence of an associated right coronary artery lesion and an ejection fraction of less than 40% (p less than 0.01). Patients with proximal LAD plus right coronary lesions had a 5-year mortality rate (34.08 +/- 8.9%) that was not significantly (p greater than 0.05) different from that of a group of 66 patients with greater than 50% narrowing of the left main coronary artery (24.02 +/- 4.3%). Thus, proximal LAD disease is more significant than is a distal lesion only in the presence of right coronary obstruction. This two-vessel combination results in a mortality rate as high as that associated with left main coronary artery obstruction.