The effect of acetazolamide, an inhibitor of carbonic anhydrase activity, on the intracellular composition of the shell gland mucosa was determined. The normal cyclic hydration of the mucosal cells was found to be reduced when the egg was in the uterus and the partition of the water between the intra- and extracellular compartments was modified. Acetazolamide decreased the accumulation of Na+ within the cells, inhibited the Na+-independent movement of Cl- and reduced the transfer of Cl- linked with Na+. It is concluded that acetazolamide blocks the intracellular generation of HCO3- and the reabsorption of Cl-.