The electrophysiological effects of parathyroid hormone (PTH) were studied in a primary cell culture model of the chick (Gallus domesticus) proximal tubule. In this model, confluent monolayers are grown on permeable filters and exhibit vectorial transport, including glucose-stimulated current. Under short-circuit conditions, PTH, at 10⁹ M, induced a positive current [short-circuit current (I_sc)] response, with an average 2-min peak response of 14.30 ± 1.58 µA/cm² over the baseline I_sc, followed by a slow decay. The PTH response was dose dependent, with a half-maximal response at 5 × 10⁹ M and maximal response at 5 × 10⁸ M. Forskolin and dibutyryl-cAMP also stimulated I_sc, as did the phosphodiesterase inhibitor IBMX. In contrast, the phorbol ester PMA inhibited baseline I_sc. The PTH response was nearly abolished by apical addition of 100 µM EIPA, an inhibitor of Na⁺/H⁺ exchangers, and partially blocked by the Cl channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB; 100 µM) and glibenclamide (300 µM). Higher doses of EIPA or NPPB alone (500 µM) were almost fully effective, with no or slight additional effects of NPPB or EIPA, respectively. The anion exchange inhibitor DIDS (100 µM) and the Na⁺ channel blocker amiloride (10 µM) had no effect. Bilateral reduction of Cl in the buffer, from 137 to 2.6 mM, abolished the PTH response; increasing Cl concentration restored the I_sc response, with a half-maximal effect at 50 mM. These data suggest that, in the chick proximal tubule, PTH activates both an Na⁺/H⁺ exchanger and a Cl channel that may be functionally linked.