The purpose of the study was to compare the effect of three intracanal medicaments on the incidence of post-instrumentation flare-ups. All teeth were instrumented to a predetermined minimum size using a 0.5% solution of sodium hypochlorite as the irrigant. Formocresol, Ledermix, and calcium hydroxide were placed in strict sequence irrespective of the presence or absence of symptoms or radiographic signs of apical periodontitis. The patients were given written post-operative instructions and a prescription for 600 mg ibuprofen to be taken if mild to moderate pain developed. If severe pain and/or swelling developed the patient was instructed to call the office immediately and was considered to have had a flare-up. Twelve flare-ups occurred in teeth with radiographic signs of apical periodontitis; none in teeth without periapical radiolucencies. Six of the twelve flare-ups occurred in retreatment cases and the other six occurred in teeth without previous endodontic treatment. No significant difference was found in the flare-up rate among the three intracanal medicaments.