Pyriproxyfen (Knack) was registered in Arizona cotton, as the crucial component of a resistance management plan, to control whitefly Bemisia argentifolii (Bellows & Perring) in 1996. A statewide monitoring program was implemented at the same time to detect and monitor whitefly resistance to this novel insecticide. Bioassays involving dipping of leaves infested with whitefly eggs showed that all Arizona whiteflies tested were highly susceptible to pyriproxyfen in 1996. The LC₅₀ estimates were in the range of 0.0020–0.0067 μg (AI)/ml. Two diagnostic pyriproxyfen concentrations, 0.01 and 0.1 μg (AI)/ml, were established for efficient identification of resistant whiteflies. No resistance to pyriproxyfen was detected in whiteflies in statewide surveys conducted in 1997 and 1998. Mean mortality at 0.01 μg (AI)/ml dropped significantly, and survivors were detected for the first time at 0.1 μg (AI)/ml in 1999, the fourth year of use of pyriproxyfen in Arizona cotton. Among the five cotton locations monitored each year since 1996, four of them had whiteflies with significantly reduced susceptibility to pyriproxyfen in 1999. Similarly, reduced susceptibility to pyriproxyfen was detected in whiteflies collected from fall melons and greenhouses in 1999. Although there have been no reports of field failures of pyriproxyfen in Arizona cotton, the reduced susceptibility of whiteflies from statewide survey in 1999 was significant. The results may indicate the development of an early stage of resistance to pyriproxyfen, and the findings should serve as early warning and substantiation of the high resistance risk of pyriproxyfen.