We studied the relationships among intimal plaque area, lumen area, and artery size in 481 sections of the left anterior descending (LAD) coronary artery taken at four standard sampling sites in 125 pressure-perfusion-fixed postmortem adult human hearts. The internal elastic lamina area was considered to be a measure of artery size or potential lumen area. Artery size correlated strongly with intimal plaque area at each LAD level (p less than 0.0001). Stepwise regression analysis revealed that plaque area was the principal determinant of artery size at each LAD level (r2 = 0.20 to 0.33). Sections of arteries with the most intimal plaque (highest quartile) were compared with those with the least plaque (lowest quartile) at each sample site. In the proximal LAD artery, the most severely diseased arteries increased in size 62% but lumen area decreased 25%. In the midportion of the LAD artery, plaque area was 10 times greater in the most diseased arteries, but lumen area remained normal because of an 80% increase in artery size. In the most severely diseased distal LAD artery sections, despite a fourteenfold increase in plaque area, lumen area almost doubled because of a marked increase in artery size. If no enlargement had occurred, the most severely diseased arteries in the proximal LAD segment would have developed a 92% lumen stenosis rather than the observed 25% lumen stenosis. In the distal LAD artery, without enlargement there would have been a 65% lumen stenosis rather than the 85% increase in lumen area that was found.(ABSTRACT TRUNCATED AT 250 WORDS)