Two new genera and three new species of large Vesicomyidae are described from cold-seep sites on pockmarks and other sulfide-rich environments in the Gulf of Guinea (tropical east Atlantic) off Gabon, Congo (Brazzaville) and northern Angola, from 500 to 4000 m depth: "Catyptogena" (s.l.) regab n. sp., Wareniconcha (n.g.) guineensis (Thiele and Jaeckel 1931), Elenaconcha guiness n.g. n. sp., and Isorropodon atalantae n. sp. For two other species already taken by the R/V Valdivia in 1898, Calyptogena valdiviae (Thiele and Jaeckel 1931) and Isorropodon striatum (Thiele and Jaeckel 1931) new localities were discovered, and the species are rediscussed. E. guiness n.g. n.sp. is also recorded from off Banc d'Arguin, Mauritania, collected by commercial fishing vessels. The vesicomyid species here treated were encountered in different depth ranges along the Gabon-Congo-Angola margin, between 500 and 4000 m depth, and it was found that, in comparison with the dredge samples taken by the Valdivia expedition off southern Cameroon and off Rio de Oro (both at 2500 m), the same species occur in other depth ranges, in some cases with a vertical difference of more than 1000 m. That means that the species are not confined to a given depth thought being typical for them and that the characteristics of the biotope are likely to play a major role in the distribution of the vesicomyids associated to cold seeps or other reduced environments along the West African margin.