The activity of cobra venom phospholipase A2 toward phospholipids in erythrocyte membranes is enhanced significantly following ghosting of the membrane. The specificity observed is phosphatidylethanolamine greater than phosphatidylcholine and is the reverse of that expected from model studies with individual phospholipids. It is shown, utilizing phospholipid mixtures, that the activity and specificity of cobra venom phospholipase A2 is dependent on the presence of other lipids and their organization.