Previous research has demonstrated active collagen synthesis in granuloma annulare (GA), a mainly degenerative disease of the skin. The present investigation is aimed to characterize details of the collagen synthesis and its regulation. Northern and in situ hybridization techniques and immunohistochemical methods are used to identify type I and type III collagen synthesis, regulation-associated polypeptides TGF-beta, Il-1 alpha, and Il-1 beta and an extracellular matrix protein tenascin, as well as lymphohistiocytic cells present in GA lesions. High mRNA levels of both pro-alpha 1 (I) and pro-alpha 1 (III) collagens were detected in GA lesions. In situ hybridization with cDNA probes revealed active fibroblasts with signals for both type I and III collagen mRNA around GA lesions. Some TGF-beta expression was found within the areas of inflammatory cells. Immunohistochemically, most of the mononuclear/lymphatic cells were CD3+ T cells. The helper/inducer phenotype (CD4+) was common among them, but there were no T-suppressor (CD8) cells. CD1+ cells were few in number, as were cells with activation or proliferation markers (CD26, CD30, and Ki67 antigens). Il-1 alpha- and Il-1 beta-positive lymphocytes/monocytes as well as interleukin-2 receptor containing cells were detected around the lesions, i.e., in the same areas as collagen-synthesizing fibroblasts. Another possible association with the regulation of collagen synthesis was the finding of an accumulation of tenascin, a growth-promoting extracellular matrix protein, in the surroundings of the GA lesions. We suggest that the firmly established and seemingly well-regulated type I and type III collagen synthesis presents a reparative phenomenon in the cutaneous lesions of GA.