Regulation of collagen gene expression was studied in fibroblast cultures established from patients with keloids, fibrotic lesions of the skin. In selected keloid fibroblast cultures, an overproduction of type I procollagen was observed. This increase was accompanied by a parallel increase in type I procollagen-specific mRNA levels, as detected by dot-blot and RNA transfer hybridizations, without concomitant change in type I procollagen gene copy number. At the same time, type III procollagen mRNA levels were unaltered, resulting in markedly elevated type I/III procollagen mRNA ratios. Thus, keloid fibroblasts offer a unique model to study the independent regulation of the gene expression of two genetically distinct procollagens, type I and type III.