Although a serum sickness-like presentation has been reported as a sequela of Hymenoptera stings, the possible role of an immune complex-mediated pathologic condition in patients receiving regular venom immunotherapy has never been addressed. To evaluate this problem, 30 adult and 15 pediatric patients receiving regular monthly doses of venom (100 micrograms of antigen) were studied. All had been receiving immunotherapy for 12 to 29 mo. At the time of venom administration, a questionnaire related to symptoms of immune complex disease was completed. A urinalysis was performed 12 hr later. In addition, blood was drawn to evaluate the presence of immune complexes by Clq and Raji cell assays. Symptom surveys revealed no clinical manifestations suggestive of immune complex pathology. All urinalyses were negative for gross and microscopic hematuria. None of the specimens was elevated on the Clq assay. Only four of the 45 patients had significantly positive Raji cell assays. Prospective reevaluation showed the presence of immune complex before venom administration, with no change in acute-phase reactants or Raji cell titers 12 hr later. Monthly administration of Hymenoptera venom appears to be unassociated with immune complex-mediated disease, by either clinical or immunologic parameters.