Immunotherapy with honeybee venom (HBV) is effective under optimal conditions, but many untoward systemic reactions are observed when venom doses are increased, especially with rush protocols. Although there were large interpatient variations, the levels of serum been venom specific IgG were found to significantly correlate with the protection of the allergic patients. A double-blind, placebo-controlled study was carried out to determine whether passive immunization with fractionated IgG from a beekeeper's serum pool was able to protect patients undergoing a rush immunotherapy program with HBV against untoward systemic reactions, and to observe if the active immunization with HBV could elicit an active IgG immune response toward venom allergens. Hyperimmune IgG was obtained from a pool of sera of beekeepers (Cohn fractions II to III) that was subsequently treated with pepsin for intravenous use. All IgG subclasses were found to be present in the preparation. Twenty-seven patients, highly allergic to HBV, were randomly allocated to two treatment groups. Twenty patients received 10 to 15 gm of fractionated IgG, and seven other patients received saline in a double-blind fashion. The next day, a 3-hour rush protocol attempted to reach a cumulative venom dose of 200 micrograms; 16/20 patients who received the fractionated IgG reached this dose without any systemic reaction, whereas none of the seven subjects who received saline could attain it, and all patients had a systemic reaction. The active immunization with HBV elicited a significant (p less than 0.05; Wilcoxon W Test) increase in venom IgG after 1 week of treatment in the patients who reached the maintenance dose.(ABSTRACT TRUNCATED AT 250 WORDS)