Neonicotinoid insecticides differ in their acute contact toxicity to honey bees. We investigated the uptake, metabolic fate, and excretion of imidacloprid and two much less toxic chemotypes, thiacloprid and acetamiprid, upon contact exposure in honey bees because ADME data for this mode of entry are lacking. Pharmacokinetic parameters were analyzed by tracking a 14C-label and by HPLC coupled to ESI-MS. Imidacloprid penetrates the honey bee cuticle much faster and more readily compared to thiacloprid and acetamiprid, thus revealing a pharmacokinetic component, i.e., faster penetration and higher steady-state internal body concentrations, contributing to its higher acute contact toxicity.