We evaluated the biological effect of IgG4 antibodies in pollinosis. We studied the ability of IgG4 to mediate histamine release by measuring anti-IgG4 in pollinic patients without previous immunotherapy. We also evaluated the modifications that sera rich in specific IgG4 and IgG itself exert upon antigen-specific histamine release. According to our results, stimulation with anti-IgG4 did not induce histamine release, as opposed to stimulation with anti-IgE, which induced histamine release in all the cases studied. On the other hand, hyperimmune sera from pollinic subjects under immunotherapy and with high levels of specific IgG4 significantly inhibited the release of antigen-specific histamine from basophils of untreated patients. After isolating IgG4 by means of affinity chromatography, preincubation of this fraction with the allergen gave rise to a significant reduction in histamine release compared to preincubation of the antigen with normal sera.