The effects of a chronic treatment with pefloxacin on aminophylline-induced seizures in genetically epilepsy-prone rat have been investigated. Two series of experiments were performed. In the first, animals received pefloxacin orally twice a day for five days, then were administered aminophylline intraperitoneally and the occurrence of seizures was evaluated. In the second series of experiments, theophylline serum concentration was evaluated in rats subject to the same experimental protocol. Pefloxacin significantly, and in a dose-dependent manner, increased the occurrence of seizure phases induced by aminophylline, but did not influence theophylline serum levels measured at different times after the injection of aminophylline. We suggest that additive neurotoxic effects of both pefloxacin and aminophylline might contribute to the increased severity of seizure score. The possible role of GABA-benzodiazepine, excitatory amino acid and purinergic mechanism, and the role of pharmacokinetic factors are discussed.