Symbioses involving sulfide-oxidizing bacteria and metazoan phyla dominate invertebrate assemblages at cold seeps and hydrothermal vents worldwide. The predominant species inhabiting cold seeps in Monterey Bay are the vesicomyid clams Calyptogena kilmeri and C. pacifica. The growth and survival of these clams depend directly upon the productivity of their chemoautotrophic endosymbionts, which is fueled by the oxidation of sulfide. For this reason, sulfide availability and sulfide-related physiology are thought to be the most influential factors governing the productivity of these associations. Both species inhabit sulfide-rich sediments and depend nutritionally on their symbionts, yet many aspects of their life histories differ considerably. Our results indicate that C. pacifica, which inhabits areas with lower environmental sulfide levels, is physiologically poised for the uptake and transport of sulfide, indicated by increased sulfide consumption rates, sulfide-binding ability, and internal sulfide levels. C. pacifica also has a greater potential for symbiont energy turnover, supported by increased sulfide oxidation potential, enzymes involved in sulfur metabolism, and bacterial densities. Conversely, C. kilmeri demonstrates a less effective sulfide uptake mechanism and, therefore, a specific need for higher environmental sulfide levels. It appears that the abilities of these 2 species to process sulfide differ greatly and reflect not only the environments in which they are found but also the capabilities of their symbionts. This research represents the first comparative investigation of the physiological functioning of closely related species in chemosynthetic symbioses and elucidates the constraints and advantages posed by different modes of sulfide (energy) uptake and assimilation in these, and perhaps other, symbiotic organisms.