Determining the way in which deleterious mutations interact in their e
ffects on fitness is crucial to numerous areas in population genetics
and evolutionary biology. For example, if each additional mutation lea
ds to a greater decrease in log fitness than the last (synergistic epi
stasis), then the evolution of sex and recombination may be favored to
facilitate the elimination of deleterious mutations. However, there i
s a severe shortage of relevant data. Three relatively simple experime
ntal methods to test for epistasis between deleterious mutations in ha
ploid species have recently been proposed. These methods involve cross
ing individuals and examining the mean and/or skew in log fitness of t
he offspring and parents. The main aim of this paper is to formalize t
hese methods, and determine the most effective way in which tests for
epistasis could be carried out. We show that only one of these methods
is likely to give useful results: crossing individuals that have very
different numbers of deleterious mutations, and comparing the mean lo
g fitness of the parents with that of their offspring. We also reconsi
der experimental data collected on Chlamydomonas moewussi using two of
the three methods. Finally, we suggest how the test could be applied
to diploid species.