n B S T R A C T External ATP causes a prompt increase in the Na and K permeability of dog red blood cells. By manipulating intra-and extracellular ion composition it is possible to observe ATP-induced net fluxes which can be explained in terms of the contribution of Na or K diffusion potentials to the membrane potential. Measurements of membrane voltage by a fluorescent dye technique confirm the existence of such potentials. A rough calculation of chloride permeability gives a value of the order of 10 -s cm/s, which agrees with results in other species. The cells appear to be somewhat more permeable to bromide than to chloride. I N T R O D U C T I O NAn interesting p r o p e r t y of dog red blood cells is that their permeability to Na and K increases on exposure to external A T P in concentrations of 0.1-1.0 mM (Parker and Snow, 1972;Elford, 1975;Romualdez et al., 1976). T h e effect is A T P specific and reversible. It can be p r e v e n t e d by including physiologic concentrations o f divalent cations in the m e d i u m and is t h e r e f o r e of uncertain significance for the cell's function in vivo. This action of exogenous A T P was first described in ascites t u m o r cells ( H e m p l i n g et Stewart et al., 1969) and has also been r e p o r t e d in isolated renal tubules (Rorive and Kleinzeller, 1972) and other tissues ( T r a m s , 1974). T h e mechanism of A T P ' s interaction with the m e m b r a n e surface is obscure.We suspected that in the presence of external A T P dog red cells might b e c o m e as p e r m e a b l e to Na and K as they are to small anions. O u r hypothesis was c o n f i r m e d by m e a s u r e m e n t s o f net ion flux and m e m b r a n e potentials. T h e data have f u r t h e r m o r e allowed us to draw some conclusions about chloride and b r o m i d e m o v e m e n t s in this species o f cell. This a p p r o a c h has p r e c e d e n t in work with cation-specific i o n o p h o r e s such as gramicidin and valinomycin (Scarpa et al., 1968; H u n t e r , 1971;Tosteson et al., 1973).It should be emphasized that the data in the present study concern net anion movements, presumably by electrodiffusion. Dog red blood cells have a tightly coupled, electrically silent anion exchange mechanism similar to that of all other species examined (Wieth et al., 1974). T h e possible relationship between net and exchange pathways will be briefly discussed in connection with o u r observations on the m o v e m e n t s o f different halide ions.