Abstract IL-4-dependent and -independent IgG1 Abs differ in their ability to induce mast cell degranulation as measured by passive cutaneous anaphylaxis (PCA). Mice immunized with OVA or PIII (fraction of Ascaris suum) produced high titers of IgG1 as shown by ELISA and PCA. In contrast, another A. suum fraction, PI, elicited IgG1 Abs with no PCA activity. IgG1 with anaphylactic activity required IL-4, as IgG1 responses to OVA and PIII in IL-4−/− mice gave no PCA. PI-specific IgG1 was IL-4-independent, because no difference was found between the responses of IL-4−/− and IL-4+/+ mice. Significant PCA reactions were elicited, however, with PI-specific IgG1 from IL-12−/− or anti-IFN-γ Ab-treated mice, although less Ab was measured by ELISA. These results indicate that one type of IgG1 has anaphylactic activity and its synthesis is IL-4-dependent, being inhibited by IL-12 or IFN-γ; the other lacks this activity and its synthesis is stimulated by IL-12 or IFN-γ.