This study was performed to examine whether a single infusion of caroverine, a quinoxaline-derivative, can be used successfully in the treatment of inner ear tinnitus. Microiontophoretical experiments in guinea-pigs have shown that caroverine acted as a potent competitive a-amino-3-hydroxy-5-methyl-4-isoxazone-proprionic acid (AMPA) receptor antagonist and, in higher dosages, a non-competitive N-methyl-d-aspartate (NMDA) antagonist. According to our working hypothesis of the pathophysiology of inner ear tinnitus (cochlear-synaptic tinnitus), these forms of tinnitus occur when the physiological activity of the NMDA and AMPA receptors at the subsynaptic membranes of inner hair cell afferents is disturbed. In total, 60 patients with inner ear tinnitus of assumed cochlear-synaptic pathophysiology were included in the study: after computerized randomization, 30 were treated with caroverine and 30 with placebo. For a response to have occurred, tinnitus had to show a reduction in both subjective rating and psychoacoustic measurement (tinnitus matching). In the caroverine group, 63.3% responded to therapy immediately after the infusion. In the placebo group, none of the patients treated showed a significant response according to the defined success criteria. The results confirm our working hypothesis on the genesis of cochlear-synaptic tinnitus.