Human placental receptors for insulin and for human basic somatomedin (BSM, analogous to human insulinlike growth factor I (IGF-I)) were selectively cross-link labelled with 125I-labelled insulin and BSM using disuccinimidyl suberate under conditions whereby cross-linking of 125I-labelled insulin to the BSM receptor and of 125I-labelled BSM to the insulin receptor was avoided. We have found that the cross-link-labelled receptors for insulin and BSM, present in equivalent amounts in human placenta membrane preparations, both cross-react with antibodies directed against purified rat liver insulin receptor. Compared with the human insulin receptor, the BSM receptor cross-reacted with the antireceptor antibody to a level of roughly 9%, indicating a limited sequence homology between the insulin and BSM receptors. Since both receptors are present in comparable amounts in solubilized placenta membrane preparations, we sought methods for the selective purification of both receptors from such extracts, so as to provide a basis for further comparative structural studies of the two receptors. We have observed that both receptors were adsorbed by affinity columns of insulin-agarose, in a manner that did not yield insulin receptor entirely free from the BSM receptor. As an alternative for receptor purification, we have found that immunoaffinity columns using antiligand antibody should provide a means for the selective isolation of cross-link labelled receptor from tissues in which both are present in equivalent amounts.