R-R variation and the Valsalva ratio are commonly used to quantitatively assess diabetic autonomic neuropathy (DAN). To assess the sensitivity of these two measures to parasympathetic ablation, 12 nondiabetic subjects were tested before and after graded doses (0.3-4.0 mg i.v.) of atropine. R-R variation was significantly reduced at 0.7 mg, whereas Valsalva ratio was not significantly smaller until the 2.0-mg dose of atropine. R-R variation continued to become progressively smaller during the 0.85-, 1.0-, and 2.0-mg doses. Valsalva ratio, but not R-R variation, was further reduced by the 4.0-mg dose. To further compare these two measures, two groups of diabetic subjects were compared with a group of nondiabetic subjects (n = 22). One group of diabetic subjects had symptoms of DAN (n = 22), and the other diabetic group had no symptoms of DAN (n = 19). In DAN subjects, both R-R variation (nondiabetic 33.2 +/- 4.3 vs. DAN 9.8 +/- 1.2, P less than .001) and the Valsalva ratio (nondiabetic 1.98 +/- 0.07 vs. DAN 1.55 +/- 0.07, P less than .001) were reduced. However, in asymptomatic subjects, R-R variation (23.2 +/- 3.9, P less than .05), but not Valsalva ratio (1.94 +/- 0.13, NS), was less than nondiabetic subjects. Even after beta-blockade, R-R variation was still less in both groups of diabetic subjects (nondiabetic 34.4 +/- 4.2 vs. DAN 7.4 +/- 1.3, P less than .001; asymptomatic 21.8 +/- 3.3, P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)