AbstractThe toxic side‐effects and anti‐inflammatory activity of combination treatment of Sprague‐Dawley rats with indomethacin and Probon, a new type of analgesic, were investigated. Following four weeks of treatment with a combination of these two drugs, the characteristic gastrointestinal side‐effect of indomethacin was markedly reduced. Mortality resulting from administration of the drug combination was significantly lower than that resulting from indomethacin treatment alone. The reduced toxicity of indomethacin in combination with Probon is probably due to a change in metabolism produced by the hepatic microsomal enzyme inducer, Probon. The anti‐inflammatory effect was also investigated using a contact thermographic method following one, three or seven days pretreatment. The advantage of this combination is that, using a higher dose of indomethacin in combination with the minor analgesic, we could achieve a more reliable anti‐inflammatory effect together with a pain‐k