We have characterized the expression of allelic variants of X-linked glucose 6-phosphate dehydrogenase (G6PD) in aorta from homozygous, hemizygous, and heterozygous baboons (Papio hamadryas). Fibrous plaques from heterozygous baboons fed a high cholesterol, saturated fat diet contained distributions of G6PD allelic variants that differed from those of normal arterial wall and fatty streaks. The skewed allelic expression patterns in fibrous plaques of heterozygotes reflect decreased cellular heterogeneity in advanced vascular lesions. The tendency toward cellular monotypism in fibrous plaques is similar to that present in advanced human atherosclerotic lesions. Our results suggest that G6PD heterozygous baboons are a unique primate model for investigating the cellular origin of proliferating smooth muscle cells in atherosclerotic plaques.