We have previously shown that, peptlde YY (PYY) receptors are widely distributed in the kidney with the greatest density located in the papilla. Systemic administration of PYY effects renal vascular and tubular function. The purpose of the present study was to determine how PYY affects electrogenic Na+ and Cl- current in inner medullary collecting duct (IMCD) cells. mIMCD-K2 cells were provided by Dr. B. A. Stanton. Short circuit currents (ISCCl, ISCNa) were measured across monolayers of mIMCD-K2 cells mounted in Ussing-type chambers. PYY had little or no effect on baseline ISCNa. Baseline chloride current in these cells is low, therefore we stimulated ISCCl with vasopressin (AVP, 1 nM). We found that PYY (1 nM). added to the basolateral membrane, caused AVP-stimulated chloride secretion to decrease by about 20%. The threshold concentration of PYY that causes an inhibition was approximately 0.1 nM. Apical applications of PYY had no effect on ISCCl. PYY also inhibits cpt-cAMP stimulated chloride currents. These findings show that PYY inhibits AVP-stimulated chloride current via receptors localised to the basolateral membrane and that part of the inhibition is mediated by actions distal lo cAMP.