We investigated the effects of aminophylline and salbutamol on tetanic force generated by the diaphragm during compensated metabolic acidosis in dogs. Anesthetized, mechanically ventilated animals were prepared with an open thorax. A cast was placed around the abdomen to maintain length and geometry of the diaphragm during contractions. A thin-walled latex balloon was positioned beneath the diaphragm to measure transdiaphragmatic pressure (Pdi). Pdi served as the index of diaphragmatic force of contraction. We measured Pdi during supramaximal phrenic stimulation at low and high frequencies and also during spontaneous inspiratory efforts for a constant diaphragmatic EMG activity. Compensated metabolic acidosis significantly reduced Pdi at all stimulation frequencies (p less than 0.05). The mean percent decrease at low frequencies was greater than at high (p less than 0.05). Pdi was decreased during spontaneous contractions as well (p less than 0.05). Administration of aminophylline significantly improved Pdi at all frequencies of phrenic stimulation (p less than 0.05) and during spontaneous inspiratory efforts (p less than 0.05). Infusion of salbutamol did not have a significant effect on Pdi at any frequency of stimulation but did produce a small potentiating effect during spontaneous contractions (p less than 0.05). We also recorded and analyzed the Pdi response to a single supramaximal impulse to the phrenic nerve, referred to as a twitch, to gain insight into possible cellular mechanisms underlying alterations in tetanic force of contraction. Compensated metabolic acidosis led to a significant reduction in peak twitch tension (PTT) (p less than 0.05) and half relaxation time (1/2RT) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)