Changes of hyperpigmentation and depigmentation in systemic scleroderma have been known since the last century, but their relationship to the pathogenesis of the condition is poorly understood. Clinical, histologic, histochemical, immunopathologic, and electron microscopic studies of the depigmented lesions in seven patients with systemic scleroderma demonstrated changes similar to those of vitiligo, but with subtle differences. Immunologic mechanisms seem to be involved in the induction of depigmentation in both vitiligo and systemic scleroderma.