Unlike its close relatives, Drosophila sechellia is resistant to the toxic effects of the fruit of its host plant, Morinda citrifolia. Using 15 genetic markers, I analyze the genetic basis of D. sechellia's resistance to this fruit's primary toxin, octanoic acid. D. sechellia's resistance is dominant in F1 hybrids between it and its sister species D. simulans. All chromosomes, except the Y and the dot fourth, carry genes affecting resistance. The third chromosome has the greatest effect and carries at least two factors. The X chromosome has an intermediate effect and harbors at least two genes, whereas the second chromosome carries at least one gene of weak effect. Thus, at least five loci are involved in this adaptation. However, I also identified large chromosome regions having no effect on resistance, suggesting that D. sechellia's resistance is neither very simple nor highly polygenic. Instead, resistance appears to have an oligogenic basis. D. sechellia's resistance to its host may contribute to ecological isolation between it and D. simulans.