1. Airway epithelium in cystic fibrosis is characterized by a defect in chloride secretion across the apical membrane and an increase in sodium absorption. The increased rate of sodium absorption can be inhibited in vitro by ouabain, a Na(+)-K(+)-ATPase inhibitor, and in cystic fibrosis patients the number and activity of nasal epithelial Na(+)-K(+)-ATPase pumps is increased. 2. We have performed a series of studies to determine whether drugs which modify airway epithelial Na(+)-K(+)-ATPase activity in vitro can modify nasal potential in cystic fibrosis patients in vivo. As transepithelial nasal potential difference measurements were used to study the effect of drug modulation of airway epithelial ion transport in vivo, the repeatability of the technique was first evaluated. In order to assess the effectiveness of the technique used for measuring nasal potential difference, a pilot study was carried out using topical amiloride, a drug which has previously been shown to inhibit airway epithelium sodium transport in vivo. We then studied the effects of ouabain and digoxin, two inhibitors of Na(+)-K(+)-ATPase, on nasal potential difference. 3. In study 1, nasal potential difference measurements were repeated on non-consecutive days in 20 patients with cystic fibrosis and 20 healthy individuals. Healthy subjects had a mean (SEM) potential difference value of -19.5 (0.9) mV with a 95% range for a single estimate of 75-133%. In patients with cystic fibrosis, the mean (SEM) potential difference was -40.4, (2.1) mV, with a 95% range for a single estimate of 74-136%.(ABSTRACT TRUNCATED AT 250 WORDS)