Blotchy is an X-linked recessive mutation at the "Mottled" locus in the mouse. The affected blotchy male (Blo/Y) mouse from an inbred genetic background demonstrates morphologic and physiologic abnormalities consistent with emphysema in adult life. Breeding of Blo/Y mice has been difficult because the inbred Blo/Y males are sterile. We report the successful development of a line of outbred Blo/Y male and Blo/Blo female nice by the controlled outcross mating of the inbred heterozygous Blo/+ female with the Argonne hybrid B6CF1 male mouse. The subsequent outcross Blo/Y progeny breed vigorously with the outcrossed Blo/+ female. The lungs of the outbred Blo/Blo female and inbred Blo/Y male mice demonstrate mild to moderate panacinar emphysema with a significant decrease in internal surface area (p less than 0.005) and an increase in mean linear intercept (p less than 0.005). In contrast, the lungs of the outbred Blo/Y is structurally normal. Despite the absence of emphysema-like changes in the outbred Blo/Y males, there were phenotypic features that suggest inherited abnormalities in connective tissue proteins including 1) high incidence of aortitis leading to premature death from aneurysmal rupture, and 2) significant decrease in the morphometrically determined parenchymal elastic fiber length in the lung (p less than 0.01). The outbred blotchy strain may be a useful experimental animal model in determining the pathogenesis of emphysema.