IgG1 and IgG4 antivenom antibody responses were compared in groups of patients who had experienced systemic reactions to wasp (Vespula spp.) or bee stings. Pretreatment serum IgG4 antibody levels were low in both groups, but IgG4 antibodies were significantly raised in bee-allergic patients (P<0.002), probably reflecting their greater exposure to stings than wasp-reactive patients. No direct or indirect relationships were found, in untreated bee or wasp patients, between IgG1, IgG4, or IgE antibody levels and the severity of a patient's last systemic reaction to a sting. After a 12-week course of venom immunotherapy (VIT), IgG1 antibodies increased significantly only in wasp-sensitive patients (P<0.001), although both groups responded with marked increases in venom-specific IgG4 (P<0.01). Wasp-allergic subjects who responded to VIT with high production of specific IgG4 showed the greatest increases (pre- to post-VIT) in IgE antibodies (P<0.05). This group also demonstrated a direct correlation (P<0.05) between post-VIT levels of IgE and IgG1 antibodies, a finding contrary to an IgE-immunoregulatory role for IgG 1. High levels of venom-specific IgG1 alone, or in combination with IgG4, were not protective in three patients who suffered repeated adverse reactions to bee VIT, showing that absolute levels of IgG subclass antivaenom antibodies are not reliably indicative of clinical responsiveness in individual patients.