We describe 2 patients with rapidly progressing systemic sclerosis that did not respond to conventional therapy, who were treated with a 5-day regimen of T cell-specific antilymphocyte globulin. One patient had deteriorating pulmonary involvement, and the second patient had developed disabling skin disease with multiple ulcers and gangrene. Both patients showed improvement concomitant with almost complete elimination of CD4+ and CD8+ T lymphocytes. Regeneration of peripheral T cells required 60-90 days and was followed by a long-term inversion of the CD4:CD8 ratio. The persistent therapeutic effect in both patients correlated with the lack of CD4+ T cells and the predominance of CD8+ T cells. This suggests a crucial role of T cell immunity in the pathogenesis of systemic sclerosis. In vitro studies of regenerating T cells demonstrated that CD4+ helper/inducer cells were functionally competent. Alterations in the composition of the CD8+ population may explain the prolonged suppression of CD4+ T cells observed during the period of therapeutic benefit.