Cutis laxa is a genetically heterogeneous connective tissue disease that occurs in both inherited and acquired forms. The most apparent defect is loose, redundant, nonresilient skin, but systemic connective tissue abnormalities exist, especially in conjunction with the early onset or autosomal recessive variety. The elastic fiber shows morphologic alterations. We studied dermal skin biopsies and cultured skin fibroblasts from 6 patients with congenital forms of cutis laxa in an effort to correlate alterations in elastin morphology and metabolism. In general, ultrastructural analysis revealed occasional variance in collagen fiber diameter, whereas elastic tissue varied in content, appearance, and the proportion and manner by which elastin and microfibrillar component associated. Fibroblast cell lines comprised of normal donors from a similar age group produced an average of 35 +/- 10 X 10(3) tropoelastin molecular equivalents per cell per hour, as measured by an ELISA. Three of six cutis laxa cell strains were markedly (5-20-fold) reduced in tropoelastin production. Two of these cell strains had specifically reduced levels of tropoelastin production relative to total protein synthesis. Analysis of elastin specific messenger RNA levels indicated this reduced expression of tropoelastin was regulated at a pretranslational level. In other strains, diminished production of elastin did not appear to be the primary defect, underscoring the heterogeneous nature of cutis laxa at both the biochemical and ultrastructural levels.