Metronidazole (Flagyl) is reduced exponentially by the contents of the rat caecum in the absence of oxygen. The rate of removal is highest at pH 7 and 37 degrees. 2. Reduction of the drug is inhibited by boiling of the caecal contents, CHCl3, Cu2+, Ag+, azodicarboxylic acid bis-dimethylamide, p-chloromercuric benzoate, N-ethylmaleimide and 4,4,4-trifluoro-1,2-thienyl-1,3-butanedione. Nitrate, ethanol (3%), CO, phenol and amytal did not affect the rate of reduction. 3. It is concluded that iron-sulphur systems are involved in degradation of the drug.