The aortic wall is nourished by diffusion from the aortic lumen and from vasa vasorum in the adventitia and outer layers of media. Intimal proliferation in atherosclerosis might be expected to reduce the effectiveness of diffusion from the lumen and increase dependence on nourishment by vasa. This study was performed to determine whether there is increased perfusion of the aortic wall by vasa vasorum in atherosclerosis. We used microspheres to measure flow through vasa in normal and atherosclerotic cynomolgus monkeys. Blood flow to inner layers of the thoracic and abdominal aorta was less than 1 ml/min × 100 g in normal monkeys, and there was a minimal increase in atherosclerotic monkeys. Flow to the outer layers of the thoracic and abdominal aorta was 1.3 ± 0.9 and 2.2 ± 0.8 ml/ min per 100 g in normal monkeys. Flow to outer layers of the thoracic and abdominal aorta was increased in atherosclerotic monkeys to 17 ± 8.9 and 31 ± 12 ml/min per 100 g (P< 0.05 vs. normal). Thus there is increased perfusion of the atherosclerotic aorta, particularly in the outer layers. During maxima] vasodilation induced by infusion of adenosine, flow through vasa was 3- to 8-fold greater in atherosclerotic than in normal monkeys. This finding suggests that proliferation of new vessels, rather than dilation of existing vessels, accounts for the increase in blood flow through vasa. We speculate that hyperemia of the aortic wall in atherosclerosis may be in part a compensatory response to increased oxygen requirements and possibly to ischemia produced by intimal proliferation and a resulting increase in diffusion distance.