We studied transepithelial potential difference (PD) in normal persons, patients with chronic disease, and patients with cystic fibrosis (CF), using the technique described by Knowles and co-workers. A maximal PD value (PDmax) and an average PD value (PDmean) were determined for each study of the nasal respiratory epithelium. The voltage response to superfusion of 10(-4) mol/L amiloride onto nasal mucosa was noted. The PD of the palm, wrist, and between two fingertips was also measured. Nasal PDmax and PDmean of the CF group were more negative than the control (P less than 0.01) and chronic disease groups (P less than 0.01). After application of amiloride, the voltage change in nasal PD was greater in the CF group than in the non-CF control groups (P less than 0.01). There were no clinically significant differences in the PD of the palm, wrist, or fingertips of the three groups. These data confirm the observation that patients with CF have hyperpolarized nasal epithelia that demonstrate greater change in response to amiloride than that in non-CF controls. These results indicate a possible role for the use of in vivo nasal PD measurements as a diagnostic test for cystic fibrosis.