The authors assessed the time of onset of the hypothermic effect of acetaminophen in 102 patients with acute ischemic stroke. These patients were randomized to treatment with either 1000 mg of acetaminophen (n = 52) or placebo (n = 50), given six times daily. Treatment with high-dose acetaminophen resulted in a 0.26 degrees C (95% CI 0.07 to 0.46 degrees C) lower mean body temperature than placebo treatment within 4 hours. This effect remained present throughout the next 20 hours. A large phase III trial seems warranted.