Salathe and Ebert ( 2003, J. Evol. Biol. 16: 976 - 985) have shown that the mean logarithmic fitness of Daphnia magna clones declined faster than linearly with increasing inbreeding coefficient F. They interpreted this result as evidence for synergistic epistasis. Trouve et al. ( 2004, J. Evol. Biol., doi: 10.1111/ j. 1420-9101.2004.00755. x) suggested that hybrid vigour could be an alternative explanation for this finding. We use a population genetic model to support the original claim that the marked deviation from linearity cannot be explained without epistasis. We further argue that the relevant reference population is the metapopulation and not the subpopulation. Taken together, we believe that synergistic epistasis between recessive deleterious alleles segregating in the D. magna metapopulation is the most likely explanation for the finding of Salathe and Ebert.