To help clarify the etiology and pathogenesis of calcific aortic stenosis, we studied retrospectively the relationship existing between that condition and two presumptive risk factors: diabetes and hypercholesterolemia. Fifty-four patients with isolated aortic stenosis, undergoing cardiac catheterization, were compared to patients without aortic stenosis who underwent angiography for unrelated reasons. The effect of diabetes and hypercholesterolemia, singly and in combination, upon the prevalence of aortic stenosis, was tested by various methods, including mathematical model fitting: Both study factors were found to be associated with aortic stenosis; their combined effect upon the prevalence of that disease appeared to be multiplicative. These findings suggest that diabetes and hypercholesterolemia may play a role in the causation of aortic stenosis. Further studies among unselected populations are needed to confirm the existence of the associations uncovered.