A two-graph Receiver Operating Characteristic analysis was done to determine the optimal cut-off value of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to Wesselsbron disease (WSL) virus. When ELISA and haemagglutination-inhibition (HI) results of WSL-positive and WSL-negative control sheep sera were compared, the sensitivity of ELISA was 97.9% and that of HI, 87.5%, while the specificity of ELISA and HI were 95.7% and 100%, respectively. The ELISA's superior sensitivity was confirmed by the results of the two assays performed on a simulated range of low-positive sera, which showed that the ELISA was able to detect WSL-antibody levels at least ten times lower than those the HI could. The ELISA was also less cross-reactive than the HI to guinea-pig antisera against nine flaviviruses relevant to southern Africa. The combination of the ELISA's ability to test untreated sera in single dilution and its superior sensitivity and lower cross-reactivity as compared to that of the traditional HI, makes it the assay of choice for automation and large-scale screening of animals for antibodies to WSL virus.