To determine the cause of the central nervous system effect of the fluorinated quinolones temafloxacin and ciprofloxacin by measuring cerebral blood flow and metabolism by use of positron emission tomography. This was a prospective, randomized, double-blind, placebo-controlled study. The patients were 13 healthy, nonsmoking volunteers whose ages ranged from 18 to 40 years. We measured brain blood flow and metabolism by use of positron emission tomography before and after a five-dose course of 750 mg ciprofloxacin, 600 mg temafloxacin, or placebo given every 12 hours. Quinolone administration produced no significant effect on visual (qualitative) reading of the positron emission tomography scans. We conclude that short-term administration of temafloxacin, ciprofloxacin, or placebo does not significantly alter cerebral glucose or oxygen metabolism. Subjects treated with ciprofloxacin demonstrated a significant decrease in brain blood flow compared with baseline and with temafloxacin- or placebo-treated subjects.