In laboratory tests, 20 strains of Aedes triseriatus differed widely in response to La Crosse virus. Infection rates ranged from 40% to 93%, and rate of transmission ranged from 20% to 90%. A control strain, tested in seven different trials, showed no significant variation in susceptibility (71–77%) or transmission ability (54–68%). A distinct geographic pattern was evident. The susceptibility and transmission rates of strains from areas where La Crosse virus is endemic were lower than that of strains from non-endemic regions, showing 71% vs. 87% for susceptibility to infection, and 46% vs. 74% for ability to transmit. Similar results have been observed in other mosquito-parasite systems, leading to the hypothesis that A. triseriatus in the upper Midwest is evolving resistance to La Crosse virus. Laboratory colonization had diverse and unpredictable effects on both transmission and infection, as might be expected with small populations and genetic drift.