Immunologic studies were performed on 11 renal specimens from seven patients with progressive systemic sclerosis (PSS). Two patients had the chronic renal lesions of PSS and five had acute PSS renal disease. One of the latter patients underwent renal transplantation after developing acute renal failure with recurrence of lesions in the allograft. The lesions in the allograft were morphologically indistinguishable from the renal lesions of acute PSS. Immunofluorescence microscopy revealed vascular localization of IgM along with early and late acting complement components C1Q, C4, and C3 in all specimens including the allograft. Fibrinogen localization was observed in the vasculature of patients with the acute form of the disease. Antiglobulin, detected by fluorescein-labeled, heat-aggregated gamma-globulin, was also present in vascular lesions from two of the specimens; Eluates of four of the kidneys including the allograft contained antinuclear antibodies. In addition, antiglobulin activity was present in eluates from three of the four kidneys, The findings suggest that (1) renal vascular lesions in PSS may result from injury via immune complexes composed of nuclear antigens and antibody, (2) the predominance of IgM in the vascular lesions may reflect the presence of rheumatoid factor in the immune complexes, and (3) a similar pathogenetic mechanism may have resulted in allograft failure following renal transplantation of a patient with PSS.