Spinosyn A, the principal component of Tracer^®; (spinosad) possesses many highly desirable characteristics for an insect control agent including pyrethroid levels of activity and a very favorable mammalian and environmental profile. However, the initial action of spinosyn A is somewhat slower than some pyrethroid insecticides such as cypermethrin. Understanding spinosyn A penetration and metabolism may provide approaches to further improving spinosad and the spinosyns as insect control agents. Studies comparing the injection versus topical toxicity of spinosyn A and cypermethrin in Heliothis virescens (tobacco budworm) larvae show that spinosyn A is as active as cypermethrin by injection, but about 5-fold less active than cypermethrin when applied topically. This apparent difference in the rate of penetration is confirmed by in vivo studies in last stadium Trichoplusia ni (cabbage looper) larvae examining the penetration of spinosyn A versus permethrin; at 4 hr posttreatment >30% of applied permethrin was internal while <10% of the applied spinosyn A was internal. Likewise, for topically applied spinosyns A, B and D, only 1.5 - 4% of the applied dose was present in the hemolymph 3 hr posttreatment. As with T. ni, radiotracer studies with H. virescens larvae showed that spinosyn A penetrates at a slower rate (2% in 3 hr) than does cypermethrin (42% in 3 hr). Studies of spinosyn A metabolism in H. virescens midguts and induced rat liver homogenates suggest that spinosyn A is highly stable to oxidative metabolism. In vivo metabolism of the acaricide, fenazaquin, and spinosyn A showed fenazaquin to be readily metabolized while there was no detectable metabolism of spinosyn A. Likewise, the co-application of piperonyl butoxide with spinosyn A did not alter activity in adult house flies while a six-fold increase in toxicity was noted with piperonyl butoxide + permethrin. Thus, available information suggests that while spinosyn A is initially slower to penetrate into lepidopterous larvae, once it is internalized it is relatively stable to metabolism thereby contributing to it's high level of activity.