T lymphocytes have been implicated in the nerve damage observed in allergic experimental neuritis and in idiopathic polyneuritis. Symptomatic autonomic neuropathy in long-standing Type 1 diabetes is a rare and unexplained complication, and some preliminary evidence has suggested a pathogenetic role for the immune system. We have measured levels of activated T lymphocytes in 18 Type 1 diabetic patients with symptomatic autonomic neuropathy and in 16 matched patients with uncomplicated Type 1 diabetes. Purified T lymphocytes from peripheral blood were stained with a fluorescein-labelled monoclonal antibody directed to the activation marker HLA-DR and counted under UV microscopy. Percent DR positive T lymphocytes were significantly raised in the patients with autonomic neuropathy when compared with long-standing uncomplicated diabetic patients (8.2 +/- 4.2 vs 4.9 +/- 3.3%, p less than 0.01). This finding lends support for a role of the immune system in the development of autonomic neuropathy.