We present information to investigate the significance of Antarctic toothfish as a prey item for Weddell seals in the Ross Sea. • We summarise the life history of Weddell seals to provide an overview of their use of the Ross Sea. As consumption of prey by Weddell seals (both the amount and type of prey) will vary between different life history stages at different times of the year in different areas, this is relevant to the question of whether seals predate significantly on toothfish. • There is evidence that Antarctic toothfish have lower densities near to seal breeding colonies in McMurdo Sound than further away (Testa et al. 1985). • Direct information on diet of the Weddell seals, including diver observations, animal-mounted camera information, and observations from field scientists in the McMurdo Sound region suggest that toothfish are a significant prey item for Weddell seals. • In contrast, research using seal stomach contents, vomit and scats provides no evidence that Weddell seals consume toothfish at all. Diver observations suggest that seals may feed selectively on only parts of toothfish so that otoliths and vertebrae may be under-represented in remains. • Indirect information using stable isotopes of carbon and nitrogen, even including recent analyses that have not been previously reported, remains inconclusive. We recommend further research using stable isotope analysis of blood samples from seals not at the breeding colonies, and samples of muscle or other slower-turnover tissue of seals at the breeding colonies. • Information from fatty acids or other biomarkers could potentially be used to investigate the importance of toothfish as a prey item for seals, but no results are available. • We have compared mortality of Antarctic toothfish in McMurdo Sound to consumption by Weddell seals. The estimates, although preliminary and subject to uncertainty, indicate that it is possible that toothfish comprise a substantial proportion of the diet of seals in McMurdo Sound between October and January. We conclude that while there is strong evidence that toothfish are a prey item for Weddell seals in McMurdo Sound between October and January, it is plausible but unproven that they are an important prey item.