A sensitive and reproducible enzyme-linked immunoassay (ELISA) for IgA class antibodies against the Delta antigen (HDAg) is described. Specificity of the assay was demonstrated by the absence of binding to an unrelated antigen or to uncoated plates and the finding that binding to HDAg was independent of total IgA concentrations in sera. Positive results were obtained with sera from 11 of 14 patients with chronic Delta virus infection (seropositive for HBsAg and IgM anti-HDAg, negative for IgM anti-HBc) at serum dilutions of up to 1:10(6). Sera from four normal healthy individuals and from 25 patients with chronic hepatitis B or other liver disorders who had no evidence of exposure to HDV were all negative in the assay.