Many juvenile hormone analogs interfere with insect metamorphosis, a property that makes them useful in insect control and as investigatorial tools with which to study metamorphic mechanisms. We report that one such analog, methoprene, interferes with mosquito metamorphic midgut remodeling. Methoprene treated Aedes aegypti (L.), Aedes albopictus (Skuse), and Culex quinquefasciatus (Say) fourth instars pupate, but the pupal midguts are morphologically similar to larval midguts. The degree of midgut remodeling is affected by the dose of methoprene applied and the extent of fourth instar development when methoprene exposure is initiated. DNA staining indicates that high methoprene concentrations interfere with diploid cell division and programmed death of polytene cells. Lower methoprene concentrations do not interfere with diploid cell division but the removal of polytene cells is incomplete. The effect of methoprene dose on the extent of midgut remodeling correlates well with its effect on pupal and adult survival. Metamorphic midgut remodeling offers a mosquito system with which to study the effect of ecdysone, juvenile hormone and juvenile hormone analogs on metamorphosis. An understanding of the molecular mechanisms by which methoprene affects mosquito metamorphosis might lead to the development of more effective mosquito control chemicals having fewer deleterious environmental effects and to genetic strategies by which mosquito populations might be controlled.