OBJECTIVE Between June 1, 1992 and August 31, 1994 we conducted an open pilot study of antithymocyte globulin (ATGAM; Upjohn, Kalamazoo, MI) in 10 patients with early systemic sclerosis (SSc) to assess whether this agent might prevent the progression of cutaneous and pulmonary involvement in this disease. METHODS Adult patients with early SSc (< 3 years) and evidence of progressive skin and pulmonary disease were enrolled. All patients were hospitalized and received a single course of intravenous ATGAM, at a dosage of 10 mg/kg over 4 hours, on 5 consecutive days. Patients were followed up at weeks 1, 2, 3, and 4, and months 2, 4, 6, and 12. Patients were considered to be improved if the Rodnan skin score decreased > or = 25%, to be worse if the skin score increased > or = 25%, and to be not improved if the skin score was within 25% of baseline. For pulmonary involvement, patients were considered to be improved if either the diffusing capacity for carbon monoxide or the forced vital capacity was increased > or = 10%, worse if decreased by > or = 10%, and stable if within 10% of baseline. RESULTS Most patients tolerated the treatment well, although 1 patient developed an allergic reaction necessitating discontinuation of treatment, 1 developed a serum sickness reaction after completion of therapy, and 1 developed a central venous access-related axillary vein thrombosis. Two patients died of SSc-related complications during the followup period. At 12 months, only 2 patients showed improvement in both skin and pulmonary function measures, whereas 5 patients were worse and 3 were stable. CONCLUSIONS At the dosage administered in this study, ATGAM appears ineffective in improving the skin and pulmonary features of SSc.