1. The effect on urate excretion of administration of probenecid and pyrazinamide was observed in normal subjects under control conditions and after induction of uricosuria by exogenous urate loading by ribonucleic acid feeding in seven subjects, by volume loading with hypertonic sodium chloride solution infusion in 11 subjects and by partial inhibition of net urate reabsorption with uricosuric drugs in 20 subjects.
2. After ribonucleic acid feeding, the uricosuric response to probenecid was intact and ribonucleic acid feeding did not produce uricosuria after pyrazinamide.
3. After volume loading, the uricosuric response to probenecid was again intact, but infusion of sodium chloride solution still produced uricosuria after pyrazinamide administration.
4. After uricosuric drugs, the uricosuric response to probenecid was diminished.
5. These responses to probenecid and pyrazinamide may reflect different mechanisms of uricosuria. Response to pharmacological inhibitors of urate reabsorption or urate secretion may be useful for classification of induced and clinical uricosuric states.