Isoflurane has been shown to depress skeletal muscle force in vitro, but data are not available regarding the effects of isoflurane on diaphragmatic muscle function in vivo. To answer this question, 15 rats anesthetized with pentobarbital and mechanically ventilated were studied. They were divided into three groups of five animals each, according to the administered concentration of isoflurane. Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 0.5 Hz, 20 Hz, 50 Hz, and 100 Hz under quasi-isometric conditions. After a control measurement (C), isoflurane was administered at a constant concentration (0.5, 1, or 1.5 MAC) and Pdi measurements were repeated after 30 min of isoflurane exposure (T1) and 30 min after discontinuing isoflurane (T2). In the group breathing 1.5 MAC isoflurane, the time constant of diaphragmatic relaxation (tau) and integrated electrical activity of the diaphragm (Edi) were also assessed. The Pdi amplitude generated by single twitch (0.5 Hz) was unchanged at the three isoflurane concentrations. A significant increase in Pdi at 20 Hz was observed at T1, which returned to control after 30 min recovery (T2). No change in Pdi during 50 Hz stimulation was noted during 0.5 and 1 MAC isoflurane exposure, whereas it was reduced at T1 during 1.5 MAC. For 100 Hz stimulation, a significant decrease in Pdi was noted for all groups at T1, which returned toward control values at T2. Edi was markedly reduced for 50 and 100 Hz stimulation, but this reduction was also transient, since Edi returned toward control values at T2.(ABSTRACT TRUNCATED AT 250 WORDS)