To determine the effect of prophylactic acetaminophen on reactions after diphtheria and tetanus toxoids and pertussis vaccination, 282 children received either acetaminophen or placebo in a double-blind, randomized fashion before and 3, 7, 12, and 18 hours after vaccination. Fever and local and systemic reactions were monitored. Switching to known acetaminophen was permitted if the patient's temperature was 38.9 degrees C or higher or for moderate pain. Overall, the reaction score of acetaminophen recipients was significantly less than that of placebo recipients. The rates of occurrence of fever and fussiness and the degree of pain at the injection site were significantly reduced by acetaminophen administration. Children who received acetaminophen were less likely to be switched to "open" acetaminophen than placebo recipients. It is concluded that prophylactic acetaminophen as given in this study had a moderating effect on fever, pain, and fussiness after diphtheria and tetanus toxoids and pertussis immunization.