To investigate collagen turnover and proliferation in dermal fibroblasts from patients with systemic sclerosis (SSc) and their relationship with disease duration and cellular subpopulations, SSc patients were grouped by disease duration (less than 2.5 years or more than 7 years). Control and SSc fibroblasts were obtained from skin biopsies. Collagen biosynthesis was determined by [14C]-proline uptake. Type I/III collagens, gelatinolytic activity, and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 were evaluated by electrophoresis, zymography, and enzyme-linked immunosorbent assay, respectively. Total collagen synthesis and the levels of alpha1(I), alpha2(I), and alpha1(III) chains, as well as TIMP-1 and proliferation were increased in fibroblasts only from patients with early-stage SSc. Gelatinolytic activity did not vary among the groups. This metabolic condition favors a higher local fibroblast population and is characterized by a heterogeneous clonal response in which the majority exhibited higher levels of collagen and TIMP-1 synthesis as well as an increase in their proliferation patterns involving hyper-reactive fibroblast subsets.