The effect of acetaldehyde on the transglutaminase activity in pooled normal human plasma has been investigated. In this study, 0.05, 0.2, and 0.7 ml of pooled human plasma were preincubated for 30 min. at room temperature with buffer or acetaldehyde at final concentrations of 40.6, 22.4, and 11.2 mM before being utilized for Factor XIIIa assay with fibrinogen and thrombin which had been preheated at 40 degrees C to destroy endogenous Factor XIII/XIIIa activity. At all concentrations of acetaldehyde and all concentrations of plasma-containing Factor XIII which were employed, prolongation of both clotting time and stabilization time was observed. The 11.2 mM acetaldehyde is within the range of daily acetaldehyde production to be predicted in severe alcoholics as a consequence of imbibing alcohol. The stabilization times measured for Factor XIIIa activity appear to be the most sensitive to acetaldehyde compared to acetaldehyde effects on thrombin, Factor Xa, and fibrinogen studied earlier in this laboratory, as well as Factors II, VII, and X.