We collected a total of 15,329 mosquitoes during weekly sampling in Davis, CA, from April through mid-October 2006 at 21 trap sites uniformly spaced 1.5 km apart over an area of approximately 26 km(2). Of these mosquitoes, 1,355 pools of Culex spp. were tested by multiplex reverse transcriptase-polymerase chain reaction, of which 16 pools (1.2%) were positive for West Nile virus (WNV). A degree-day model with a developmental threshold of 14.3 degrees C accurately predicted episodic WNV transmission after three extrinsic incubation periods after initial detection. Kriging interpolation delineated that Culex tarsalis were most abundant at traps near surrounding agriculture, whereas Cx. pipiens clustered within residential areas and greenbelt systems in the old portion of Davis. Spatial-temporal analyses were performed to test for clustering of locations of WNV-infected dead birds and traps with WNV-positive Cx. tarsalis and Cx. pipiens; human case incidence was mapped by census blocks. Significant multivariate spatial-temporal clustering was detected among WNV-infected dead birds and WNV-positive Cx. tarsalis, and a WNV-positive Cx. pipiens cluster overlapped areas with high incidences of confirmed human cases. Spatial analyses of WNV surveillance data may be an effective method to identify areas with an increased risk for human infection and to target control efforts to reduce the incidence of human disease.