We used an indirect immunofluorescence test with Giardia lamblia trophozoites as antigen to detect anti-G. lamblia antibodies in serum. Seventy-one patients and control subjects were studied in a blinded protocol. Titers in 29 of 30 patients with syptomatic giardiasis (1:16 to 1:1024) did not overlap titers in 19 healthy control subjects (1:2 to 1:4): titers in 15 patients with hookworm. Entamoeba histolytica, or intestinal bacterial overgrowth were 1:16 or less. Absorption of giardiasis patients' sera with G. lamblia trophozoites but not with E. histolytica, Trichomonas vaginalis, or Escherichia coli reduced the titers to, or nearly to, control values. Titers in individual sera were 93.9% reproducible within a fourfold or less dilution. Our results indicate that G. lamblia, an intestinal parasite often regarded as noninvasive, induces a systemic antibody response. The indirect immunofluorescence test for anti-G. lamblia antibodies is specific and reproducible; it may be useful in epidemiologic and immunologic studies of giardiasis.