Disposition kinetics of nonsteroidal, anti-inflammatory tiaprofenic acid (1) and its metabolites were studied in healthy subjects and arthritic patients under treatment with 200 mg of the drug three times daily. The concentration of the drug and its metabolites were measured using a sensitive and specific HPLC method. The pharmacokinetics of tiaprofenic acid in arthritic patients seems to be similar to those in healthy subjects. The drug is rapidly absorbed, extensively bound to plasma proteins and, upon repeated administration, is accumulated in the body only to a limited extent. While only unchanged drug was found in plasma, a negligible amount of the unchanged drug was recovered from urine. The major pathway of drug elimination seems to be through conjugation. The reduced and oxidized metabolites of 1, 2 and 3, respectively also are found in urine as conjugates. The conjugates are, however, relatively unstable and are readily hydrolyzed to their parent compounds upon storage or addition of alkali. As elimination of the drug is dependent upon urinary excretion of the conjugates, it may be influenced by reduced renal function or the presence of other drugs.