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Abstract:  Aquagenic wrinkling of the palms (AWP) is a cutaneous phenomenon marked by the transient formation of edematous, translucent papules and plaques on the palms and fingertips within minutes of water exposure. AWP is anecdotally reported in patients with cystic fibrosis (CF) and several studies have recently confirmed this association. The primary aim of this study was to determine the prevalence of aquagenic wrinkling of the palms in subjects with cystic fibrosis (CF) compared to controls, and secondarily to evaluate for genotype-phenotype correlations among CF subjects found to have AWP. Fifty-one children with CF and 25 control children who were being treated for asthma underwent a 5-minute hand immersion in lukewarm water. The test for AWP was positive if subjects demonstrated >30% wrinkling over the palm. Secondary analyses explored associations with genotype, pancreatic and pulmonary function, body mass index (BMI), and sweat chloride levels. Palmar transepidermal water loss (TEWL) was also measured for all subjects with and without AWP. Forty-three of the subjects (84%) with CF demonstrated aquagenic wrinkling, in contrast to none (0%) of the controls. These results remained statistically significant when stratified for by age and race. TEWL was significantly higher in CF subjects with AWP compared to CF subjects without AWP and controls. No genotype-phenotype correlations were detected in patients with AWP, nor were there associations of AWP with other phenotypic features of CF, although these analyses were likely underpowered. Aquagenic wrinkling of the palms is prevalent in children with CF and is associated with increased TEWL.