We propose a statistical model for dissecting a multilocus genotypic value into its main (additive and dominant) effects and epistatic effects between different loci in a case–control association study. The model can discern four different kinds of epistasis, additive×additive, additive×dominant, dominant×additive, and dominant×dominant interactions. To test each kind of epistasis, a χ 2 test statistic was computed for a two by two contingency table derived from combined genotypes in both case and control groups. We derived an analytical approach for estimating the asymptotic distribution of the χ 2 test statistic for epistatic tests under the null hypothesis, with the result being consistent with that from Monte Carlo simulations. The new model was used to analyze a case–control data set for candidate gene studies of stroke, leading to the identification of several significant interactions between causal SNPs on this disease.