Patients with cystic fibrosis have characteristic disturbances in the electrolyte composition of their sweat, saliva, and pancreatic secretions. We studied the electrical properties of sweat glands in eight patients with cystic fibrosis and in seven normal volunteers to determine the basis of the well-documented inhibition of sodium absorption in this disease. The average electrical potential across 47 sweat glands in the patients was -66.3 +/- 2.1 mV, as compared with -29.8 +/- 3.2 mV for 39 glands in the normal controls (P less than 0.001). The average sweat-secretion rate in 33 glands from six patients was not significantly different from that in 34 glands from six controls, but average concentrations of sodium, chloride, and potassium were significantly higher in sweat droplets from the patients. Calculated rates of both sodium and chloride reabsorption were lower in sweat glands of patients than of normal controls, but chloride reabsorption was more markedly reduced than sodium reabsorption. We conclude that a decrease in epithelial permeability to chloride may explain the characteristic changes in sweat electrolytes in cystic fibrosis and could be a generalized abnormality in the disease.