Abstract: The recent emphasis on understanding and identifying larvicide resistance in mosquito populations has resulted in a nationwide investigation of product susceptibility profiles. One striking result from these studies is the broad range in observed lethal doses for active ingredients (AI) in different mosquito species. Is this evidence of resistance to or tolerance of the product? We use results from Lysinibacillus sphaericus dose-response studies, observations of mosquito control operations, field experiments, and in-lab assays performed in Connecticut, U.S. to make the argument that larvicide dosage relationships can be species-specific and are, in some cases, indicative of AI ineffectiveness or tolerance. Specifically, we show that L. sphaericus is highly lethal to Culex pipiens mosquitoes in both controlled and applied settings while L. sphaericus is ineffective for container breeding Aedes spp., such as Aedes albopictus and Aedes triseriatus, as well as Culiseta melanura. While these results demonstrate the proof of principle for L. sphaericus specificity in Culex spp. mosquitoes, further research is needed to identify the chemical, physiological, and molecular basis for such species-specific relationships as well as strategies for effective control of non-Culex or mixed genus larval habitats.