BACKGROUND: To describe immune and endocrine responses in severe hymenoptera hypersensitivity requiring venom immunotherapy (VIT) during in vitro fertilization (IVF). CASE PRESENTATION: A 39-year old patient was referred for history of multiple miscarriage and a history of insect sting allergy. Four years earlier, she began subcutaneous injection of 100 mcg mixed vespid hymenoptera venom/venom protein every 5-6 weeks. The patient had one livebirth and three first trimester miscarriages. Allergy treatment was maintained for all pregnancies ending in miscarriage, although allergy therapy was discontinued for the pregnancy that resulted in delivery. At our institution ovulation induction incorporated venom immunotherapy (VIT) during IVF, with a reduced VIT dose when pregnancy was first identified. Serum IgE was monitored with estradiol during ovulation induction and early pregnancy. Response to controlled ovarian hyperstimulation was favorable while VIT was continued, with retrieval of 12 oocytes. Serum RAST (yellow jacket) IgE levels fluctuated in a nonlinear fashion (range 36-54%) during gonadotropin therapy and declined after hCG administration. A healthy female infant was delivered at 35 weeks gestation. The patient experienced no untoward effects from any medications during therapy. CONCLUSION: Our case confirms the safety of VIT in pregnancy, and demonstrates RAST IgE can remain <60% during IVF. With proper monitoring, VIT during IVF can be safe and appropriate for selected patients and does not appear to adversely affect blastocyst implantation, early embryo development or perinatal outcome. Further studies will be needed to develop VIT guidelines specifically applicable to IVF.