To evaluate the development of autonomic neuropathy, 23 patients with a moderate (group A) and 18 patients with a long (group B) duration of diabetes and without symptoms of autonomic neuropathy were re-investigated 6 yr after the initial studies. Autonomic nerve function was evaluated from heart reactions to deep breathing (E/I ratio) and to a rapid 90° tilt (acceleration and brake indices). Symptoms of autonomic neuropathy (SAN) developed in 18 patients (nine in each group) who showed a low mean E/I ratio and brake index in both studies. In group A, but not in group B, patients with SAN showed a decrease in the acceleration index and most SAN patients (8/9) in group A had an abnormal acceleration index in the follow-up study. We conclude that in both groups SAN developed rapidly and was preceded by decreases in E/I ratio and brake index.