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Cefamandole (CMD), a betalactam antibiotic with a l-methyl-tetrazole-5-thiol group, evokes in man a disulfiram-like alcohol incompatibility with flush, tachycardia, hypotension and nausea (1, 2). An accumulation of acetaldehyde (ethanol metabolite) is thought to be responsible for these symptoms (disulfiram-like reaction). This explanation is derived from an increase in the acetaldehyde concentration found in the blood of alcoholized experimental rats after pretreatment with CMD (3-5). The increase of the acetaldehyde concentration in blood is caused by an inhibition of aldehyde dehydrogenase (ALDH) by CMD, as found in vitro with low-K m ALDH preparations from rat liver (5). The inhibition of the ALDH activity is of a competitive character, as shown by the results of our enzyme-kinetic investigations ( Figure 1). Our experiments were carried out with isolated ALDH from the livers of female Sprague-Dawley rats (230 g; breeding station and holding conditions described elsewhere [6]) using a conventional method (7) modified as follows: The hepatic microsomes and mitochondria containing fraction (preparation described previously [8]) were resuspended in a 3% EDTA solution (for inactivation of NADH-consuming systems) with glutathion (0.6%; for protection against ALDH oxidation) and ultracentrifuged (105,000 x g; 30 min; 4°C). The sediment was resuspended in an Na-phosphate buffer pH 7.4 (0.2 m) containing 1% Triton (to solubilize the ALDH from the lipid membranes of the cell organelles), and ultracentrifuged (105,000 x g; 30 min; 4°C) again after one hour (0°C). The amount of protein in the ALDH containing supernatant was determined (standard: albumin, bovine, fraction V; Sigma, St. Louis/U.S.A.) with Folin reagent