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A protein-electrophoretic analysis of six putative morphospecies in the bivalve family Vesicomyidae from eight deep-sea hydrothermal vent sites in the eastern Pacific, three cold-water seep sites in the eastern Pacific and the Gulf of Mexico, and one whale-carcass site off Southern California revealed electromorph patterns diagnostic of 10 vesicomyid species. Electrophoretic patterns for 14 enzymes encoded by 17 presumptive gene loci were scored in all 10 species. The pairwise genetic distances (Nei's D) for these 10 species ranged from 0.857 to 2.792, values within the range expected for distinct species and genera. However, the degree of genetic divergence among these taxa could not be used for phylogenetic inferences because allozyme differences had in many cases reached evolutionary saturation. Notwithstanding, the present results revealed a significant problem with current morphospecies identifications of these clams and with applications of the current generic names Calyptogena and Vesicomya. Given the cryptic nature of these taxa, we suggest that subsequent studies simply refer to these clams as “vesicomyids” until careful morphological analyses and molecular studies are completed and systematic relationships are clarified.