Effect of the use of 4-hydroxyantipyrine, the metabolite of aminopyrine and antipyrine, with aminopyrine, antipyrine, and 4-iso-propylantipyrine, the antifebrile-analgesic of the pyrazolone system, on the metabolsim of these principal agents was examined by the measurement of the metabolic rate and rabbit blood level of the principal agents, using rat liver specimens, 9000xg supernatant fraction of the liver, and rabbit liver specimen. 1) Metabolism with rabbit and rat liver rspecimens showed the inhibitive effect of 4-hydroxyantipyrine against aminopyrine and antipyrine, but only slight on 4-iso-propylantipyrine. 2) Metabolism of principal agents by the 9000xg supernatant fraction from rat liver was inhibited by 4-hydroxyantipyrine. 3) Continued administration of 4-hydroxyantipyrine and antipyrine failed to show any phenomena for induction of drug metabolizing enzyme. 4) Blood level of principal agents in rabbit was maintained when 4-hydroxyantipyrine was administered orally in combination rather than when those were administered alone. These results indicated that 4-hydroxyantipyrine possessed the effect of inhibiting the metabolism of pyrazolone series agents.