Confluent human epithelial cell cultures derived from the reabsorptive sweat duct have proven to be a stable experimental model with basic electrophysiological properties identical with the native organ, when grown on a permeable support and mounted in an Ussing chamber. Using these techniques, the effect on electrical parameters of isoproterenol stimulation was studied on cultures from normals and patients with cystic fibrosis. The responses to isoproterenol of the two groups differed entirely in nature. In normals the transepithelial resistance decreased because of increased chloride conductance without engaging active transport processes. In patients the opposite situation was observed. The results indicate a defect localized in the intracellular transformation of the isoproterenol stimulus in cystic fibrosis.