We compared the dose-response relationships and the neuromuscular blocking effects of mivacurium and rocuronium after chronic isepamicin therapy for 7 days in 56 anesthetized rabbits. Train-of-four stimuli were applied every 10 s to the common peroneal nerve, and the force of contraction of the tibialis anterior muscle was measured. Chronic isepamicin therapy is associated with a rightward shift of the mivacurium and rocuronium dose-response curves. The effective dose for 50% twitch depression of mivacurium and rocuronium increased significantly, from 16.9 +/- 4.8 and 56.5 +/- 5.3 microg/kg, respectively, with placebo to 30.6 +/- 5.3 and 75.6 +/- 4.7 microg/kg, respectively, during isepamicin therapy. The isepamicin rabbits receiving mivacurium 0.18 mg/kg or rocuronium 0.6 mg/kg had an accelerated recovery from neuromuscular blockade compared with those receiving placebo. The results of this study show that mivacurium and rocuronium have both a decreased effect and a shorter duration of action in rabbits when used during concurrent isepamicin therapy. We studied the dose-response relationships and the neuromuscular blocking effects of mivacurium and rocuronium during chronic isepamicin therapy in rabbits. Mivacurium and rocuronium have both a decreased effect and a shorter duration of action during chronic aminoglycoside antibiotic therapy in rabbits.