A three-way crossover study was undertaken in 10 healthy subjects to characterize the reported disulfiram-like activity of moxalactam and to assess its influence on ethanol and acetaldehyde metabolism. On different occasions separated by at least 2 wk subjects were given in random order: 0.5 gm/kg ethanol orally, 0.5 gm/kg ethanol followed in 1 hr by 1.0 gm IV moxalactam, and 1.0 gm IV moxalactam every 8 hr for four doses followed by 0.5 gm/kg ethanol. Mean ethanol elimination rates of 13.1 +/- 0.76, 10.1 +/- 1.11, and 10.9 +/- 1.06 mg/dl/hr (mean +/- SEM) were observed in the three protocols, respectively. Corresponding mean estimated acetaldehyde clearance rates were 103.7 +/- 15.55, 92.8 +/- 13.79, and 97.3 +/- 10.41 l/min (mean +/- SEM). While no consistent moxalactam effect on ethanol or acetaldehyde elimination was observed, two subjects experienced mild disulfiram-like reactions to ethanol after moxalactam pretreatment. In one subject this reaction was associated with markedly elevated blood acetaldehyde concentrations. We conclude that moxalactam pretreatment may induce a disulfiram-like reaction after ethanol ingestion in some, probably due to inhibition of aldehyde dehydrogenase, and that alcoholic beverages are contraindicated in patients receiving moxalactam. We suggest, however, that such reactions will not occur when moxalactam is given after ethanol ingestion.