We describe four patients who had seizures while receiving ofloxacin; no other causes were evident. Common factors among all patients included advanced age and use of a high-dose regimen. The renal insufficiency of three patients and the timing of the seizures implicate accumulation of ofloxacin as a contributing factor. Other potentially related factors included electrolyte abnormalities and prior neurological insult. Improved awareness of and further investigation into the neurotoxic effects of ofloxacin may enhance its safe use.