Morphologic studies and postmortem arteriograms provide qualitative evidence that atherosclerosis induces neovascularization in coronary arteries. In this study we obtained the first measurements of blood flow through vasa vasorum in atherosclerotic coronary arteries. We measured blood flow with microspheres to intima media and to adventitia in normal and atherosclerotic cynomolgus monkeys. Blood flow to adventitia was not altered by atherosclerosis. The blood flow to intima media, however, was increased more than fivefold by atherosclerosis: flow was 3 +/- 1 in normal animals and 16 +/- 5 in atherosclerotic monkeys (p less than 0.05). Blood flow was threefold greater in atherosclerotic than in normal coronary arteries during adenosine-induced vasodilatation, which suggests that proliferation of new vessels, not dilatation of existing vessels, accounts for the increase in flow through vasa in intima media. Histologic studies indicated that vasa vasorum to intima media in atherosclerotic coronary arteries originate from adventitial vasa. We conclude that: 1) there is a large increase in blood flow through vasa vasorum to intima media, but not to adventitia, in atherosclerotic coronary arteries; and 2) increased flow is produced primarily by proliferation of new vessels that originate from adventitial vasa.