Tienilic acid (ticrynafen) [2,3-dichloro-4-(2-thyenil-carbonyl) phenoxyacetic acid] is a new diuretic with uricosuric properties in man and dog. In this animal the drug acts by blocking tubular transport of uric acid in the proximal tubule. We have demonstrated that tienilic acid (TA) is highly bound to plasma proteins at 37 ¤C (more than 95% at drug concentrations of 3.0–20.0 mg/dl). Thus, glomerular filtration of the drug is negligible and tienilic acid must reach the kidney at the antiluminal site of the tubule. During free-flow studies, the clearance of tienilic acid at stable plasma concentrations ranging from 3.0 to 20.0 mg/dl ranged from 11 to 22% of glomerular filtration measured by exogenous creatinine clearance. These values are 3–5 times greater than that accounted for by filtration of the drug alone and are highly suggestive of tubular secretion. Secretion becomes more apparent during alkalinization of the urine when the clearance of tienilic acid may rise to 40 and even 100% of glomerular filtration. During stop-flow studies, the urine over plasma ratio of the drug (U/P TA) over that of creatinine (U/P Cr) decreased along the nephron indicating progressive reabsorption. At equivalent plasma concentration, it was demonstrated that tienilic acid markedly depresses PAH transport in the proximal tubule. When plasma tienilic acid concentration is kept low (5 mg/dl) and PAH concentration is raised to 30 mg/dl, the (U/P TA)/(U/P Cr) drops by 50%. Our results indicate active secretion of tienilic acid in the proximal tubule followed by passive pH dependent reabsorption along the nephron. The drug is transported through the common organic acid pathway by a carrier having higher affinity for tienilic acid than for PAH.