AbstractEpistasis contributes significantly to intrapopulation variation in floral morphology, development time, and male fitness components of Mimulus guttatus. This is demonstrated with a replicated line-cross experiment involving slightly over 7000 plants. The line-cross methodology is based on estimates for means. It thus has greater power than the variance partitioning approaches historically used to estimate epistasis within populations. The replication of the breeding design across many pairs of randomly extracted, inbred lines is necessary given the diversity of multilocus genotypes residing within an outbred deme. Male fitness is shown to exhibit synergistic epistasis, an accelerating decline in fitness with inbreeding. Synergism is a necessary, but not sufficient, condition for a mutational deterministic hypothesis for the evolutionary maintenance of sexual reproduction. Unlike male fitness measures, flower morphology and development time yield positive evidence of epistasis but not of synergism. The results for these traits suggest that epistatic effects are variable across genetic backgrounds or sets of interacting loci.