Autonomic function was followed in 8 chronic uremic patients on periodic hemodialysis over a period of almost eight years. The cardiovascular autonomic testing included R-R interval variation test, deep breathing, Valsalva manoeuvre, heart rate and blood pressure responses to standing, sustained handgrip. The patients were investigated on entry into the study and after 18, 56, and 92 months. Six months after the study at time 56 months, they switched from acetate to bicarbonate dialysis. The response to deep breathing test was significantly reduced at time 18 months versus baseline (P = 0.014), but significantly increased at time 92 months versus 56 months (P = 0.042). A significant decrease was found in the systolic blood pressure response to standing between baseline and 18 months (P = 0.014) and in the response to handgrip test between 18 and 56 months (P = 0.014). Multivariate analysis of the autonomic tests by a pattern recognition method (Bayesian analysis) showed that, at the time of entry into the study, two out of eight patients had autonomic damage. At 18 and 56 months, 6/8 patients had autonomic dysfunction. At the last time of investigation, 30 months after the onset of bicarbonate dialysis, all the patients showed a reversal of autonomic damage. Age and duration of dialysis on entry did not affect autonomic function. The present study is the first demonstration that autonomic neuropathy can recover after long-term dialysis. Since chronic hypoxemia is a cause of polyneuropathy, we postulate that: 1) hypoxemia in dialysis patients may have a role in the pathogenesis of uremic polyneuropathy, and particularly of autonomic dysfunction; 2) in patients on bicarbonate dialysis, a greater hemodynamic stability with less hypoxemia may lead to a recovery of autonomic function.