Changes in the distribution and quantity of different collagen types in some internal organs was determined in tissues from patients with systemic sclerosis. In addition, sera from patients with systemic sclerosis were assayed for circulating anti-collagen antibodies and were compared with normal sera. The results of a specific immunohistological survey of skeletal muscle and kidney showed a general increase in type I and III collagens in the fibrotic lesions when compared with age matched normal tissue. A thickening of basement membranes was also observed. Biochemical quantitation of the ratio of types I and III collagens in normal and affected kidney showed up to a three-fold increase in type III compared to type I collagen, consistent with the immunohistological data. Finally, quantitation, by the ELISA technique, of circulating anticollagen antibodies in sera from patients with systemic sclerosis demonstrated positive results for types I, III and IV collagens when compared with normal controls. These results are discussed in relation to the clinical progression and possible mechanisms of pathogenesis of the disease.