We determined whether detection of antibody response against a newly detected epitope, designated Em18, among Echinococcus multilocularis antigens could be a reliable marker for differentiation of active cases of alveolar hydatid disease (AHD) from inactive cases. Fifteen Alaskan patients with either active or inactive lesions of AHD previously confirmed clinically, pathologically, and serologically by the Em2-enzyme-linked immunosorbent assay (ELISA) were used for a blind test by Western blotting. Ten and five cases were considered to be active and inactive cases, respectively. One of the 10 cases classified serologically as active was judged to be inactive based on clinical and pathologic criteria; the patient had a recognizable parasitic lesion, and following short-term treatment with albendazole, a biopsy of the liver showed a degenerated lesion that did not grow in rodents. The five cases judged to be inactive included two confirmed inactive cases with cicatrized lesions and three active cases that showed the weakest values in the Em2-ELISA. The most predominant IgG subclass responding to Em18 was IgG4. In general, there were good correlations between 1) the antibody response against Em18 and the presence of active lesions and 2) the antibody response against Em18 and the Em2-ELISA values.