Abstract:The mechanism by which phospholipase A2 (EC 3.1.1.4) inhibits the binding of 3H‐saxitoxin (STX) to membranes from lobster walking‐leg nerves was examined. It was concluded that this inhibition of the binding was due to the accumulation of unsaturated fatty acids and lysophosphatides, products of the lipase action, in the 3H‐STX binding site. The destruction of the lipids themselves did not appear to cause the loss of the binding. The following evidence was presented in support of these conclusions. (1) Among the phospholipases tested, phospholipase A2 was the most effective in inhibiting the binding. Phospholipase A2 is also the only lipase that produces fatty acids and lysophosphatides. (2) The addition of fatty acid‐free bovine serum albumin protected the 3H‐STX binding sites from the inhibitory action of phospholipase A2; fatty‐acid‐free bovine serum albumin is capable of binding free fatty acids and lysophosphatides, thus preventing these products from interacting with the STX binding sites. (3) The addition of exogenous unsaturated fatty acids or lysophosphatides to membrane material inhibited the binding. These findings show that the STX binding activity is sensitive to unsaturated fatty acids and to lysophosphatides.