The objective of this study was to determine the role of atrial natriuretic peptide (ANP) in autonomic neuropathy and to learn the effect of saline solution infusion on ANP. Twenty one subjects were distributed in three groups: 1) control group, 2) diabetic patients with autonomic neuropathy, and 3) diabetic patients without autonomic neuropathy. The levels of ANP, renin, aldosterone and cortisol were determined at baseline and 30, 60, and 75 min after saline infusion. At baseline ANP was lower in diabetic patients with autonomic neuropathy (32.9 +/- 13) than control group (34 +/- 15). ANP increased statistically significantly at 30 min after solution administration in control group (60 +/- 35, F = 4, p < 0.05), but it did not change in diabetic patients (Group II: 34.3 +/- 9.3 and Group III 34.6 +/- 10.7). Sixty and 75 min after saline infusion ANP returned to basal levels in control group, but they did not change in diabetic patients. A delayed response of renin, aldosterone and cortisol to saline solution administration was observed in diabetic patients. There was no correlation between ANP levels and alteration of autonomic tests. It is concluded that independent of autonomic neuropathy, the levels of ANP did not increase with saline infusion in diabetic patients.