The recently developed Og4C3 ELISA, which detects circulating Wuchereria bancrofti antigen, appears promising for use in epidemiological surveys, but its sensitivity is unknown in persons with ultra-low microfilarial densities. We used the Og4C3 to test the sera of 282 persons who were microfilaria-positive in 1-16 ml of blood, 18 persons who were microfilaria-negative but who had ultrasonographic or biopsy evidence of adult W. bancrofti infection, and 63 lifelong residents of a non-endemic area of Brazil. A total of 276 (97.9%) persons with detectable microfilaraemia tested positive (optical density > 0.033). At microfilarial densities of < 1, 1-30, and > 30 microfilariae per ml of blood, the sensitivity of the Og4C3 was 72.2, 97.6 and 100%, respectively (chi 2-test for trend, P < 10(-6)). The assay was positive in 66.7% of amicrofilaraemic persons with evidence of adult worm infection and in one (1.6%) of 63 residents of the non-endemic area (specificity, 98.4%). Our findings support the increasingly widespread use of the Og4C3 for field investigations and epidemiological assessments. However, the sensitivity of the assay may be low in persons who are microfilaria-negative or with densities of < 1 microfilaria per ml.