Improvement of cochleovestibular symptoms induced by trimetazidine (TMZ) has been evidenced by clinical studies. However, a poor knowledge of the physiopathology and the scarcity of experimental models contributed to making determination of the mode of action of the drugs difficult. We studied the effect, in vitro, of TMZ on the production of oxygen-derived free radicals using, as a biological model, the isolated semicircular canal of the frog. This model allows to exert separate control over the ionic composition of the endo- and perilymphatic fluids. The spontaneous activity of the afferent nerve fibers, as well as the endolymphatic potential, were recorded at rest. Three additional parameters were analyzed, while the semicircular canal was subjected to mechanical stimulation, i.e., ampulla potential, nerve potential and the evoked frequency of action potentials. Free radical generation induced by the administration of phenazine methosulfate (PMS, 10(-5) M, 15 min) into the perilymphatic compartment, leads to a deterioration of the production of endolymph and the release of this afferent neuromediator. Inversely, PMS has no influence whatsoever on the mechanisms of mechanical-electrical transduction. The addition of TMZ (10(-6) or 10(-5) M) in the perilymphatic compartment counteracts the harmful effects of free radicals on the various bioelectric activities. These results suggest that the beneficial action of TMZ observed during treatment of cochleovestibular disorders is due, at least in part, to the anti-oxidizing properties of the molecule of interest.