Nine skin biopsies from seven herpes gestationis patients were studied by immunofluorescence (IF) techniques. Basement membrane zone (BMZ) deposition of C3 and properdin was present in all nine skin specimens, while IgG deposition was apparent in only one. With in vitro C3 IF staining, positive BMZ staining (HG factor activity) was noted with all seven of our patients' serum samples tested. By standard indirect IF staining, however, only one of these serum samples contained BMZ antibodies of the IgG type. Two cord serum samples, tested by these same methods, yielded positive in vitro C3 staining (HG factor activity) but negative indirect IF staining (IgG). HG factor activity was found to be stable at 56 degrees C for 30 min and in two of three specimens at 56 degrees C for 1 h. Treatment of the complement source (normal human serum) used in the in vitro C3 staining assay with Mg2-EGTA or use of C2-deficient serum as the complement source inhibited HG factor activity. HG factor blocked the specific staining of the BMZ of normal human skin by labeled bullous pemphigoid antibodies. By sucrose density gradient ultracentrifugation and gel chromatography (Sephadex G-200), HG factor activity eluted with IgG-containing fractions. The highly purified IgG fraction of two herpes gestationis sera was also positive for HG factor activity. Our studies suggest that HG factor is an IgG antibody that may not be demonstrable by conventional IF methods, but which activates the classical complement pathway.