Significant and specific binding of intrinsic factor-cobalamin occurred in proximal but not in the distal half of the intestine in an adult marsupial, the American opossum. 2. The purified opossum kidney receptor, like rat and canine kidney receptors, revealed a single band of M(r) approximately 230 on SDS-PAGE. However, unlike the rat and canine receptors, the opossum receptor was sensitive to both Endoglycosidase H and peptide-N-glycosidase F. 3. The opossum intrinsic factor-cobalamin receptor demonstrated a ten-fold higher affinity for intrinsic factor-cobalamin complex when the source of IF was from the opossum pancreas, rather than rat stomach. 4. The opossum kidney receptor had low immune-crossreactivity with anti-serum raised to rat and canine kidney receptor. 5. These studies suggest that intrinsic factor-cobalamin receptor expressed in the American opossum, though conserved, appears to be structurally different from the rat and canine receptors.