Gene expression of collagens VI, I, and III in Werner's syndrome was studied by measuring messenger RNA (mRNA) and protein production levels in four fibroblast strains from patients with Werner's syndrome and comparing them with age-matched healthy subjects. Levels of type VI collagen mRNA were decreased in all Werner's syndrome fibroblast strains and the decreases were in parallel in all three chains (alpha 1, alpha 2, and alpha 3) of type VI collagen. A coordinate increase of the alpha 1(I) and alpha 1(III) collagen mRNA levels was observed in three of the four Werner's syndrome fibroblast strains. However, no qualitative abnormality of these mRNA transcripts in Werner's syndrome fibroblasts were found by Northern blot analysis. Changes in type VI and type I collagen mRNA correlated well with production levels of corresponding proteins, as determined by immunologic assays. These data suggest that there are changes in expression of multiple connective tissue constituents in Werner's syndrome fibroblasts.