Cystic fibrosis is the most common fatal genetic disease affecting caucasians and is perhaps best characterized as an exocrinopathy involving a disturbance in fluid and electrolyte transport. A high NaCl concentration in the sweat is characteristic of patients with this disease; the basic physiological reason for this abnormality is unknown. We have microperfused isolated sweat ducts from control subjects and cystic fibrosis patients, and report here results which suggest that abnormally low Cl- permeability in cystic fibrosis leads to poor reabsorption of NaCl in the sweat duct, and hence to a high concentration of NaCl in the sweat.