Peripheral blood mononuclear cells (PBMC) obtained from scleroderma patients and normal controls were cultured in the presence of types I and IV collagen, intima collagen, laminin, and phytohemagglutinin. PBMC from 9 of 19 patients (47%) demonstrated lymphocyte transformation in response to laminin, and those from 2 of 17 patients (12%) demonstrated reactivity to type IV collagen. None of the patient PBMC were responsive to type I collagen or to intima collagen. Healthy controls failed to demonstrate lymphocyte transformation in response to laminin or collagens. Analysis of clinical data, including age, disease duration, and degree of skin thickening and internal organ involvement, failed to predict the response to laminin or type IV collagen. The significance and disease specificity of this cellular immunity to laminin and, with lower frequency, to type IV collagen, that occurs in some scleroderma patients are unknown.