We performed quantitative immunohistochemical studies of sural nerve biopsy specimens from 20 patients to determine whether endoneurial and epineurial lymphocytic infiltration occurs in diabetic nerves. The diabetic nerves contained a mean of 129 CD3+ cells per tissue section compared to 19 cells in patients with chronic neuropathy matched for the histologic severity of disease, and 0-5 cells in normal control nerves. The T-cell infiltrates in the diabetic nerves were predominantly of the CD8+ cell type. Activated endoneurial lymphocytes expressed immunoreactive cytokines and major histocompatibility class II antigens. Microvasculitis was found in 12 (60%) patients. Infiltrative T cells may contribute to the pathogenesis of diabetic neuropathy through a variety of effector mechanisms.