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1. It is well known that red blood cells suspended in isotonic NH4Cl solution swell because penetration of NH3 induces a transmembrane exchange between Cl-o and OH-i(or HCO3-i). The rate of swelling thus depends on the speed of the transmembrane exchanges and on the amount of anions available for exchange. 2. It has been demonstrated in experiments carried out in a CO2-free medium that OH-ions are poorly permeating whereas the permeability for HCO3-is very high. Thus the rate of swelling is largely dependent on the intracellular HCO3-concentration. In this context the well-known inhibitory effect of sulphonamides upon swelling can be interpreted, and always has been until now, as being due to the inhibitory action of the drug on the intracellular carbonic anhydrase. However, this inhibitory effect could also result from a direct action of the drug on the transmembrane exchange; it would explain why under conditions of total carbonic anhydrase inhibition we have shown that the inhibition of swelling is far from maximal. 3. A direct experimental evidence of such an effect of carbonic anhydrase inhibitors on the transmembrane exchange of Cl-with HCO3- was obtained with benzolamide (Cl 11,366), Cl 13,580 and ethoxzolamide. Surprisingly enough, however, acetazolamide (Diamox) does not affect the transmembrane exchange process. 4. The inhibitory effect of sulphonamides on HCO3-transport process is discussed in terms of an interaction of the drug with a transport system common to HCO3- and organic anions.
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