A woman with atopic dermatitis experienced anaphylactic episodes following intercourse with her husband, with subsequent exacerbations of her atopic dermatitis. Skin testing and an in vitro leukocyte histamine release assay established the diagnosis of immediate hypersensitivity to her husband's seminal fluid; delayed hypersensitivity to seminal fluid could not be demonstrated. Antigen was found in the seminal fluid of nonrelated men. Radioallergosorbent testing detected the presence of circulating IgE antibodies specific for seminal plasma protein. Immunotherapy with seminal plasma may have limited the severity of a subsequent reaction. Serum from the husband and nonrelated men also contained antigen that provoked histamine release from the patient's leukocytes in vitro. The antigen in serum was associated with the globulin fraction and had a temporal relationship to ejaculation, appearing within 12 hours of ejaculation and disappearing within four days.