Na⁺ and Cl^– currents were studied in primary cultures of human nasal epithelium derived from non-cystic fibrosis (non-CF) and cystic fibrosis (CF) patients. We found that Na⁺ absorption dominates transepithelial transport and the Na⁺ current contains an amiloride-sensitive and amiloride-insensitive component. In non-CF tissue both components contribute about equally to the entire short-circuit current (I_SC), whereas in CF tissues the major part of the current is amiloride-sensitive. Na⁺ removal reduced I_SC to values close to zero. Several Cl^– channel blockers were used to identify the remaining tiny Na⁺-independent current. Under unstimulated, physiological conditions in the presence of Cl^– on both sides and amiloride on the apical side of the epithelium diphenylamine-2-carboxic acid (DPC), 4,4′-diisothiocyanatostilbene-2,2′- disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) failed to induce clearcut inhibition of I_SC. cAMP as well as ATP did not affect I_SC either in CF or in non-CF epithelia. Reduction of apical Cl^– increased I_SC and depolarized transepithelial potential; however, the observed increase was insensitive to DIDS, DPC and NPPB. From these data we conclude that Cl^– conductances in primary cultures of human nasal epithelium derived from CF patients as well as from non-CF patients are present only in low numbers or do not contribute significantly to transepithelial ion transport.