Eastern Equine Encephalitis (EEE) was in Cuba before the 1940s; the virus has been isolated from horses, birds, and rodents during epizootic as well as interepizootic periods. The only isolation of Western Equine Encephalitis (WEE) virus was from a sick pigeon found in the vicinity of Havana University. Both viruses can cause human disease; the isolation of WEE virus from the centre of an urban area emphasises the need for the prompt isolation and rapid identification of these agents. The object of this work was to compare the sensitivity of a continuous cell line (XL-2) from the toad, Xenopus laevis, with primary chick embryo cell cultures (CEC) routinely used for isolation as well as assay of these viruses. Both cell systems were infected with EEE virus isolated from horse brain and WEE virus isolated from a sick pigeon. A clear cytopathic effect (CPE) consisting of rounding and detachment of cells was observed in both cell cultures infected with the two viruses. By 18 hours post-infection, there was partial destruction of the cell monolayer and by 24 hours the CPE was total. The infectious titre of EEE and WEE viruses in XL-2 and CEC were similar. Both viruses produced small plaques (0.5-1.0 mm diameter) in XL-2 cells. Studies on the sensitivity of the XL-2 cells for direct isolation of the two viruses from field samples and for the detection of Cuban flaviviruses by the immunofluorescence test are in progress.