The metabolism of a novel polyvalent saluretic agent (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196) was studied in the chimpanzee. Following oral administration, 50% of the radioactive dose was recovered in the urine in 4 days; 8-14% of the dose was excreted as unchanged drug. The fecal specimens accounted for 5-9% of the dose. Following i.v. administration an initial rapid elimination of drug from the plasma was observed [(t1/2 half life).alpha. .apprx. 0.4 h, (t1/2).beta. .apprx. 4 h]. The data are consistent with the rapid elimination of radioactivity, .apprx. 30% of dose, in the urine during the 1st 24 h, followed by a much slower rate of excretion of drug and metabolites. These findings are congruous with the high affinity (> 98%) of MK-196 and the major metabolite with plasma proteins. The urinary metabolites were isolated and identified by the following techniques: solvent extraction, column chromatography, TLC, GLC, derivatization, and mass and NMR spectroscopy. The major metabolite, which resulted from p-hydroxylation of the 2-phenyl substituent, accounted for about 40% of the urinary radioactivity. Reduction of the ketone group, methylation of the p-hydroxy group, and additional phenyl ring hydroxylation were also shown to occur. There was no evidence for glucuronide formation nor did SKF-525-A [proadifen hydrochloride] inhibit the metabolism of the drug in the chimpanzee. Under conditions of induced metabolic alkalosis, the urinary levels of MK-196 increased from 11 to 40%. Probenecid and p-aminohippurate administered during metabolic alkalosis decreased the clearance of drug (40-15%).