Water immersion-induced skin wrinkling (WISW) is dependent on intact peripheral sympathetic function. WISW was hypothesized to reflect autonomic function in subjects without peripheral neuropathy. We prospectively studied 70 healthy subjects (aged 31 +/- 8 years, 63% females) without cardiovascular risk factors or neurological disease. All subjects underwent short-term heart rate variability (HRV) studies. Time and frequency domain variables were derived including the HRV index. WISW was graded using a previously validated scale of 1-4 of which 18.6% of subjects exhibited grade 1 (minimal) WISW and 35.7% had grade 2 WISW. On multivariate analysis using the HRV index, WISW was independently related to height and the HRV index. We conclude that WISW is related to central autonomic function.