A radioiodinated derivative of OS2 (125I-OS2), a neurotoxic monochain phospholipase A2 isolated from taipan venom, was previously found to bind to a specific brain membrane receptor with very high affinity. 125I-OS2 is now used to identify the properties of neurotoxic phospholipase receptors in other tissues. Heart, skeletal muscle, kidney, lung, liver, pancreas, and smooth muscle membranes also contain high-affinity binding sites for toxic phospholipases A2. In most tissues, two different types of receptor sites have been characterized for 125I-OS2 with Kd1 and Kd2 values in the 1-5 pM and the 10-50 pM range respectively. Whereas all receptors are similar in the different tissues in terms of their affinity for 125I-OS2, maximal binding site capacities were very different, varying from 1.3 pmol/mg of protein in brain to 0.01 pmol/mg of protein in pancreas. In brain, heart, and skeletal muscle, receptor densities vary with in vivo development. Affinity labeling experiments have identified the subunit composition of OS2 receptors and indicated that these receptors do not have identical structures in the different tissues. Binding competition studies with OS2 and other toxic phospholipases showed tissue-dependent pharmacological profiles. All these results taken together suggest the existence of a family of receptors for neurotoxic phospholipases.