Hypersensitivity to human seminal plasma is rare, but probably under-diagnosed. It should be suspected in women with unexplained anaphylaxis, vulvo-vaginitis, pelvic pain and dyspareunia. The diagnosis relies on the clinical presentation, the exclusion of other causes, a positive skin test result to seminal plasma and the detection of IgE directed to allergenic proteins (such as prostate specific antigen). Use of condoms is the best preventive measure. Premedication with antihistamines or anti-inflammatory agents is often unreliable. Some patients may benefit from intra-vaginal or subcutaneous desensitization procedures to seminal plasma, which then require to measures to uphold tolerance. In case of pregnancy wish, artificial insemination or in-vitro fertilization with spermatozoids is an alternative to desensitization.