The rate of exchange of bicarbonate and chloride ions across the red cell membrane was studied in a continuous flow rapid reaction apparatus at 37 degrees C. A transmembrane gradient both ions was produced by mixture of cells suspended in a solution of one ion with an isosmotic solution of the other ion. Carbonic anhydrase activity was inhibited by acetazolamide to prevent changes in CO2 concentration during the experiments. Chloride and bicarbonate efflux from cells were studied in separate experiments at each experimental pH. Using a least squares technique, values of chloride and bicarbonate permeabilities were fitted to each pair of independent experiments. Chloride permeability averaged 1.1 (+/- 0.2 SD) X 10-4 cm/s and was not affected by change in pH. Recovered bicarbonate permeabilities varied widely, always remaining at least fivefold greater than chloride permeability. While bicarbonate permeability could not be accurately characterized, it appears to be greater than chloride permeability. Analysis of CO2 transfer with the estimated permeabilities indicates that the bicarbonate-chloride exchange by itself probably does not limit CO2 transfer.