Five patients with seizures related to imipenem administration are described. The potential of imipenem therapy to cause seizure was further studied in a mouse model and compared with the potential for seizure with penicillin and cefotaxime therapy. Penicillin caused ataxia and seizure at a mean mouse serum level of 5800 microns/mL, cefotaxime at 3400 microns/mL, and imipenem at a much lower serum concentration of 1900 microns/mL. The potent activity of imipenem therapy against bacteria, allowing for a clinical dose of only 2 g/d, is unfortunately offset by its higher propensity to induce neurologic symptoms in humans and mice at much smaller doses than would therapy with penicillin G or the cephalosporins, such as cefotaxime.