The effects and interactions of metabolic and respiratory acid-base changes on electrically-evoked twitch response, train-of-four and tetanic stimulation with pipecuronium (Pip), vecuronium (Vec) and atracurium (Tra) were studied in the isolated rat hemi-diaphragm preparation. pip (3X10(-7) - 4X10(-6) M), Vec (3X10(-6) - 15X10(-6) M) and Tra (10(-6) - 3X10(-5) M) decreased the electrically-evoked (phrenic nerve stimulation, 0.1 Hz, 0.2 ms, 10 V) twitch response in a dose related fashion and Pip was more potent than Vec and Tra. In the alkali state (pH 7.6 or high HCO3 ), the decrements of twitch response, train-of-four and tetanus ratio induced by Pip (1.5uM) were potentiated, but the effects of Vec or Tra were markedly intensified by acid midium (pH 7.2 or low HCO3 ). And also, decreasing pH by increasing PCO2 or by decreasing HCO3 intensified the effects of Vec and Tra, whereas it reversed by Pip. Conversely, increasing pH by decreasing PCO2 or by increasing HCO3 antagonized the effects of Vec and Tra, whereas it potentiated the Pip effect. On the basis of these finding, the result of the present study suggest that neither PCO2 nor HCO3 has a specific action, but that changes in pH may be responsible for the results. In addition, the differences of the above results by each drugs may not be due to the number of quaternary ammonium of the agents. And also, indicate that the effective site of the influence of the acid-base change upon the neuromuscular blocking effects might be prejunctional nerve terminal.