Hypersensitivity to human seminal fluid is rare but can be life threatening. We report a case of IgE-mediated anaphylaxis to seminal plasma that was diagnosed by skin prick tests and successfully treated by local desensitization. A 32-year-old woman suffering from angioedema and hypotension after exposure to semen was treated with epinephrine upon admission. Skin prick tests and immunoblotting for IgE binding components showed that she was sensitized to her husband's seminal plasma. Local desensitization, which persisted for six months, was achieved by intravaginal administration of serial dilutions of her husband's seminal plasma.