The milkweed-oleander aphid, Aphis nerii (Boyer de Fonscolombe) (Homoptera: Aphididae), feeds on different milkweed species in northern California than in Puerto Rico. The hosts vary, primarily between regions, for both identity and quantity of cardenolides that the aphid sequesters for its own defense. In tests for hostassociated fitness trade-offs only one case was found in which host plant and fitness corresponded, but the effect was not significant. However, power to detect fitness trade-offs was limited and the possibility of considerable differences in fitness on a particular host for aphids from different hosts cannot be excluded. On Californian host species, among which migration is common, generalized host use could result from selection for general-purpose genotypes. However, this explanation cannot apply to generalized host use of Californian and Puerto Rican milkweeds because the regions are isolated by distance. A cardenolide sequestration mechanism that is free of substantial energy costs could provide the basis for fitness homeostasis on variable host plants that makes trade-offs unlikely even on hosts from different regions.