Technical Abstract: Aedes aegypti (L.) is the primary vector of both dengue and yellow fever. Using insecticides is one of the major ways to control this medically important insect pest. However, few new insecticides have been developed for mosquito control in recent years. As a beginning of our collaborative effort to search for new insecticides to control mosquitoes, piperidine was used as base compound for further optimization. Herein, we report the structure-activity relationships of 33 piperidines against female Ae. aegypti. On the basis of 24-h lethal dose(50%) value after topical application, the most toxic compound was 2-ethyl-piperidine, with an lethal dose(50%) as low as 0.8 micrograms per mosquito. The toxicities of piperidine derivatives were significantly decreased when a benzyl moiety was attached to the carbon of the piperidine ring, with an lethal dose(50%) value as high as 29.2 micrograms per mosquito. The toxicity order of three moieties attached to the carbon of the piperidine ring was: ethyl- > methyl- > benzyl- derivatives. When the same moiety was attached to the piperidine ring, the carbon position to which the moiety was attached conferred different toxicity and the toxicity order was: 2nd carbon > 3rd carbon > 4th carbon. Taken together, these preliminary results may be useful in guiding further piperidine ring modifications in the development of potential new insecticides.