Seventeen patients with Dupuytren's contracture underwent partial fasciectomy, and frozen tissue sections from the involved palmar fascia were prepared for binding studies with hybridoma-derived murine monoclonal antibodies (MoAb) recognizing connective tissue differentiation antigens. The two MoAb used were both generated using human sarcomas as immunizing agents, 23H7 known to bind to an antigen shared by selected sarcomas and carcinomas but not normal adult tissues except a subset of granulocytes, and 12C9 shown to recognize a common fibroblastic marker. MoAb 23H7 was discovered to bind to a subset of fibroblasts within the lesions of six of 17 patients with Dupuytren's disease. Occasionally it immunostained a single cell population associated with tissue granulocytes dispersed in the surroundings of the lesions. MoAb 12C9 was found to be expressed in only 12 of 17 specimens prepared from involved lesions from Dupuytren's disease. It is suggested that fibroblasts from selected patients with Dupuytren's contracture express a novel antigen, defined by MoAb 23H7, previously shown to be associated with human sarcomas and other neoplasia. The other fibroblast marker which is defined by MoAb 12C9 and known to be a common connective tissue antigen, is only occasionally expressed in lesions involved with this disease. Though additional markers associated with Dupuytren's contracture remain to be defined, the MoAb, capable of defining connective tissue differentiation markers, reported in this study may serve as new immunological probes for immunodissecting this syndrome into subsets of diseases which may better define the variety of clinical patterns presented by patients.