The effect of ethanol and acetaldehyde on the activity of a range of intracellular cytoplasmic and lysosomal proteolytic enzymes has been determined in human brain, liver and skeletal muscle tissues in vitro. There was a substantial degree of inhibition for most protease types in all tissues if sufficiently high concentrations of ethanol (10%, v/v; 1.7 mol/L) or acetaldehyde (1%, v/v; 0.17 mol/L) were used in the assay media. However, it was concluded that direct inhibition of proteases in vivo by ethanol or acetaldehyde is improbable, at the concentrations of these agents likely to pertain in vivo, and that any effect of these agents on intracellular protein catabolism must occur via a more subtle biochemical mechanism.