Benzolamide (CL-11,366), a potent carbonic anhydrase inhibitor, was used to examine the influence of carbonic anhydrase inhibition on the reabsorption of chloride, sodium, and bicarbonate in the rat proximal convoluted tubule. Administration of 2 mg/kg benzolamide was associated with a decrease in the tubular fluid/plasma (TF/P) chloride ratio from 1.19+/-0.10 (SEM) to 1.06+/-0.01, and an increase in the TF/P bicarbonate ratio from 0.181+/-0.02 to 0.584+/-0.02. This dose of benzolamide significantly reduced proximal fractional reabsorption of chloride by 29.14%, of sodium by 34.3%, and of bicarbonate by 35.64%. These results indicate that benzolamide administration inhibits the reabsorption of all three electrolytes in the proximal convoluted tubule. Although 20 mg/kg benzolamide accentuated the changes in fractional reabsorption, the differences between 2 and 20 mg/kg were not statistically significant. Inhibition of proximal tubular cytoplasmic and luminal carbonic anhydrase could well explain the diminished bicarbonate reabsorption and a fraction of the diminished sodium reabsorption noted in these studies. The fall in chloride reabsorption, and a portion of the fall in sodium reabsorption, however, may be a direct or indirect consequence of carbonic anhydrase inhibition or of an influence of benzolamide on a transport mechanism not dependent upon carbonic anhydrase.