A semi-isolated population of Culex tarsalis in Kern County, CA was found to vary significantly in its seasonal and yearly susceptibility to peroral infection with western equine encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses during the breeding seasons of 1975–1981. Female cohorts of the population were significantly more resistant to WEE virus from 1975 through 1977 than from 1978 through 1981. On the average, females were 40 times more susceptible to WEE virus during May than during August. Increases in resistance correlated significantly with the number of days accrued from April through June, when daily ambient air temperatures equaled or exceeded 26.7°C or 32.2°C, respectively. Analyses of data on WEE viral susceptibility, temperature, and rainfall for the 7 year period suggested that Cx. tarsalis should be most susceptible to infection in years with wet winter-early spring periods followed by cool springs. However, inconsistencies in the expression of WEE viral susceptibility during mid- to late summer of some years indicated that other unidentified extrinsic factors, in addition to temperature and rainfall, may induce changes during preimaginal development that affect the peroral susceptibility of adult females. Seasonal and yearly changes in the susceptibility of the Cx. tarsalis population to per os infection with SLE virus did not necessarily occur at the same time as those observed with WEE virus and did not appear to correlate with changes in ambient air temperature. Thus, extrinsic factors that affect the expression of viral susceptibility of Cx. tarsalis, and perhaps the genetic basis of viral susceptibility, apparently differ for WEE and SLE viruses.