Densitometric analysis of [35S]methionine-labeled dermal fibroblast proteins by two-dimensional protein gel electrophoresis revealed that cultures derived from abdominal wall and the anterior aspect of lower leg skin exhibit different patterns of specific protein synthesis. Moreover, the response to interferon-gamma is dependent upon the anatomic site of culture derivation. Plasminogen activator inhibitor type-1 is expressed constitutively in fibroblasts from both sites. However, interferon-gamma (100 U/ml) treatment for 48 h resulted in an up-regulation of the polypeptide in leg cultures and a marked inhibition of expression in fibroblasts from the abdomen. A number of other protein spots became more or less abundant in cultures from the two sites following treatment with the cytokine. It would appear that dermal fibroblasts from the abdominal wall and leg differ intrinsically in regard to their protein synthetic repertoires and their responses to interferon-gamma. These findings may be relevant to the pathogenesis of Graves' dermopathy where the skin of the lower leg becomes infiltrated with glycosaminoglycans and other extracellular material.