Insecticide resistance and cross-resistance was determined for three strains of Culex quinquefasciatus Say in the southeastern United States. HAmCq and MAmCq strains were collected in 2002 from Huntsville and Mobile, AL. The VBFmCq strain was collected in 1998 from Vero Beach, FL. VBFmCq, HAmCq, and MAmCq larvae showed resistance to permethrin with resistance ratios of 13, 100, and 940, respectively, compared with the susceptible S-Lab strain. Levels of resistance in HAmCq and MAmCq larvae were 200- and 830-fold to resmethrin and 4- and 70-fold to malathion, respectively. VBFmCq, HAmCq, and MAmCq strains all demonstrated a great ability to develop tolerance and/or cross-resistance to different insecticides, including deltamethrin (50-, 100-, and 300-fold), chlorpyrifos (150-, 33-, and 720-fold), fipronil (10-, 5-, and 15-fold), and imidacloprid (7.5-, 5- and 10-fold, respectively). Comparison of resistance ratios for pyrethroids, organophosphates, and imidacloprid at LC₅₀ and LC₉₀ and gradual slopes of dose-response curves indicated that VBFmCq, HAmCq, and MAmCq were heterozygous in response to these insecticides. All three strains showed high levels of susceptibility to Bacillus thuringiensis variety israelensis (Bti) and spinosad, although these mosquitoes had been extensively exposed to Bti. Thus, we conclude that Bti and spinosad may be valuable for the management of Cx. quinquefasciatus, especially in situations where local strains are highly resistant to other insecticides.