Fingertip skin wrinkling after prolonged immersion in water is a well-recognized phenomenon, whereas a denervated digit does not exhibit normal skin wrinkling while a finger with a regenerated or repaired nerve shows at least partial reappearance of wrinkling. This is the basis for the bedside immersion-wrinkling test of autonomic digital nerve function. The exact mechanism of fingertip skin wrinkling is still subject to controversy. The purpose of this study was to investigate the relationship between the tonicity of a solution and the time elapsed to skin wrinkling. Fourteen healthy volunteers (28 hands) were recruited for investigation. We submerged all 28 hands in solutions of varying tonicity while maintaining all other parameters constant. We found that increased tonicity significantly slowed the time to wrinkling (TTW). Hypotonic solutions such as water should be used when performing clinical bedside testing for autonomic digital nerve function.