After prolonged selection, two hybrid strains of Culex tarsalis were evolved that were highly resistant to infection following ingestion of western equine encephalomyelitis virus. These strains were greater than 25,000-fold more resistant than the most susceptible parental strain when fed on viremic chicks. Resistance was associated with a mesenteronal barrier since both refractory and parental strains were equally susceptible to infection by intrathoracic inoculation. Susceptibility was dominant, possibly incompletely dominant, over resistance. Inheritance was probably polyfactorial but this could not be determined with certainty since a small proportion of individuals appeared to become infected by nongenetic mechanisms.