The mode of inhibition of Triton WR 1339 (oxyethylated t-octylphenol polymethylene polymer) on postheparin lipolytic activity and on lipoprotein lipase activity of heart, adipose tissue and liver has been studied in the mouse in vivo and in vitro. The low enzyme activity observed in the acetone powder extracts of the tissues of triton-treated mouse, which had no measurable triton levels together with the significant reversal of triton-inhibition in vitro by increasing concentrations of enzyme, suggested that the primary action of the detergent is on the enzyme per se.