From October 1962 to August 1964 Venezuelan equine encephalitis (VEE) virus could be isolated from the far northwest to the far northeast of Venezuela. Isolation and identification of VEE virus was achieved within 42 hours after receiving human serum and brain samples by simultaneous isolation and protection tests in BHK21 cells. Subsequent collections of sera from man and animals were investigated serologically by HI and neutralization tests. HI and neutralizing antibodies decreased rapidly in man. The reservoir for VEE could not be established, although antibodies were found in several different animal species. Many goats had antibodies. No antibodies were found in birds, which therefore may be regarded as having been unimportant as hosts in this epidemic. VEE virus was isolated most frequently from Aedes taeniorhynchus, and also from Aedes serratus, Anopheles aquasalis, Psorophora confinnis and, for the first time, Aedes scapularis. Exceptionally heavy rainfalls in 1962 resulted in total annual precipitation double that of the average for the preceding 5 years, providing ideal breeding conditions for mosquitoes and crowding animals on reduced unflooded areas. These factors may have contributed to the onset of the epidemic.