BACKGROUND Wrinkling of the skin of the palm and sole is considered to be dependent on the presence of intact sympathetic nervous activity. Loss of sympathetic integrity could be simply and usefully assessed by the absence of wrinkling. To test this hypothesis, the skin wrinkle test was compared with the starch-iodine sweat test and sympathetic skin response (SSR) in patients with abnormal sympathetic function. METHODS The three tests were carried out in 34 patients (68 limbs) undergoing temporary or permanent disruption of the sympathetic chain to upper or lower limbs. Included in this group were six diabetics undergoing chemical or surgical sympathectomy, lumbar epidural infusions following vascular surgery, and patients for whom sympathectomy was being considered. Sensitivity and specificity analysis and predictive values of the wrinkling response and the starch-iodine test were related to the SSR as the standard. RESULTS The wrinkle test showed a sensitivity of 97% and specificity of 95%, and bore good correlation to the SSR. The starch-iodine test showed sensitivity of 55% and specificity of 93%. A hypothesis for the mechanism of wrinkling based on the observations of the present study is proposed. CONCLUSIONS The wrinkle test is a reliable test of sympathetic function, is inexpensive and is easy to perform at the bedside. The sweat gland myo-epithelial cells and absence of sebum could play an important role in the wrinkling response. It can be used to select patients who will benefit from sympathectomy, and can adequately evaluate sympathetic blockade.