Negative cross-resistance refers to a situation in which an insect population that is tolerant (resistant, virulent) to one insecticide is hyper-sensitive (avirulent) to a second insecticide and insects hyper-sensitive to the "rst compound are tolerant to the second. Most research dealing with negative cross-resistance has focused on the molecular biology and chemical aspects of this phenomenon. We explored, from a population genetics perspective, whether negative cross-resistance is feasible in the control of an insect population. As a "rst step towards this goal, we used a deterministic approach to evaluate di!erent control scenarios and to identify some of the potential limitations of negative cross-resistance strategies. Speci"cally, we investigated how such approaches could be used in a host-plant resistance program. Homoand heterozygous insect "tness in#uenced the e!ectiveness of the toxins in controlling the insect population. The negative cross-resistance strategy was most useful when the insects' virulence to both host-plant toxins was recessive. When virulence was dominant, there were many periods when intervention with an outside (or third) class of compounds, which had a di!erent mode of action than that of the negative cross-resistance compounds, was needed to control the insect population. The greater the number of insect generations per plant generation, in the absence of immigration or emigration in the insect population, the greater the requirement for intervention with a third class of compound to maintain e!ective control of the insect population. When the toxins were rotated every insect generation, and virulence in the insect was recessive to both toxins, e!ective control of the insect population was maintained without intervention of a third class of compounds.