Colorado potato beetle, Leptinotarsa decemlineata (Say), adults and larvae collected from Long Island, NY, were 100.8 and 13.2 times more resistant to imidacloprid, respectively, compared with a susceptible strain. This high level of resistance appeared in only the third field season of imidacloprid use. Analysis of probit lines from F₁ reciprocal crosses indicated that resistance to imidacloprid in adults was inherited autosomaly as an incompletely recessive factor. The degree of dominance of the resistance was −0.23 and −0.10, respectively, 3 and 7 d after treatment (incompletely recessive). The χ² analysis of response ratio statistics from F₁ × susceptible back crosses compared with a monogenic model suggested that more than one locus is responsible for resistance to imidacloprid. Synergism studies with piperonyl butoxide suggested that mixed-function oxidase mediated detoxification is responsible for the resistance to imidacloprid in adults. Synergism studies with S,S,S-tributyl phosphorotrithioate (DEF) indicated that esterase mediated detoxification may be an additional resistance factor. Mixed-function oxidase mediated detoxification is probably also one of the mechanisms of resistance to imidacloprid in larvae. Because the synergists used did not completely eliminate resistance in the resistant strain, there may be additional mechanisms involved. Refugia and crop rotation decrease the frequency of homozygous resistant genotypes and may be effective resistance management strategies, because of the recessive nature of the resistance.