Several reports have yielded conflicting results on the role of IgG4 antibody on the surfaces of target cells in immediate type allergy. This study was performed to elucidate whether IgG4 antibody inhibits IgE-mediated histamine release from target cells after antigenic stimulation, and whether it has reaginic activity. Serum was obtained from patients with nasal allergy receiving specific immunotherapy for housedust and mites. IgE and IgG4 were enriched affinity chromatographically using monoclonal antibodies to IgE and IgG4, respectively, from the pooled sera. Both fraction revealed high antibody activity to Dermatophagoides Farinae antigen. Peripheral blood leukocytes from three non-allergic donors were passively sensitized with 100 or 300 micrograms of IgG4 according to the method of Levy and Osler with a slight modification. Minimal or no histamine release was observed from leukocytes after challenge with both mite antigen and anti-IgG4 monoclonal antibodies. Furthermore, to investigate the reaginic activity of IgG4, leukocytes from patients with nasal allergy were stimulated with anti-IgG4 antibodies. The leukocytes of only three out of twenty patients released up to 10% histamine regardless of the IgG4 concentration, while the other patients' leukocytes released minimal amounts of histamine. Two of the three above-mentioned non-allergic donors were passively sensitized with 100 or 300 micrograms of IgG4 either one hour after sensitization with 100 ngs of IgE or simultaneously with the same amount of IgE. After sensitization with 100 ngs of IgE, one showed high-grade histamine release after challenge with 0.5 micrograms/ml mite antigen and the other showed middle-grade release with 0.1 micrograms/ml mite. With the presence of 300 micrograms of IgG4, histamine release was significantly inhibited in both donors regardless of the manner of sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)