Anaphylactic sensitivity to her husband's seminal fluid occurred in a 46-year-old woman six weeks after a hysterectomy. Her husband was azoospermic as a result of an elective vasectomy. A pooled sample of his seminal fluid was used for skin and laboratory tests. Fractionating (Sephadex G100) chromatography was also performed on his seminal fluid. The patient showed positive intracutaneous skin tests to his unfractionated seminal plasma and a Sephadex G100 fraction designated No. 3. This fraction was also passively transferable to a nonallergic volunteer and it stimulated histamine release from the patient's leukocytes. The dose-response effects of this fraction compared with unfractionated seminal plasma in these assays showed greater bioactivity. After informed consent was obtained, the patient was immunized to fraction 3 in a classic desensitization protocol. Two weeks after the final dose of immunotherapy, intercourse was performed without condoms in a medical facility and under the supervision of a physician. No adverse symptoms were experienced by the patient on this occasion. Regular and frequent sexual activity is required to maintain her tolerant state.