BACKGROUND Allergen-specific immunotherapy (SIT) is a well-documented treatment for allergic rhinitis, asthma, and allergy to bee venoms. Side-effects of SIT in long-term have not been well documented yet. Herein, we report a case of Sjögren's syndrome following SIT. METHODS The patient, a 25-year-old Caucasian woman, was started on subcutaneous grass-pollen immunotherapy. The patient's autoantibodies before the SIT screening tests were negative. We determined that anti-extractable nuclear antigen (ENA) was positive (ENA = 98.4, normal range 0-25 U) on routine screening tests at 44 weeks of her treatment, and then SIT was discontinued. The patient complained of burning and itching in her eyes for 6 months. Schirmer's and salivary flow tests were positive. Although antinuclear antigen and rheumatoid factor were negative, anti-SS-A/Ro was positive. Viral hepatitis markers were negative. Minor salivary-gland biopsy was performed, which showed grade 4 sialoadenitis. The HLA type of the patient was B55 (B22), Bw6, Cw1 for class I and DR11, DR52, DQ7 (DQ3) for class II. After the immunotherapy had been stopped, there were no changes in the symptoms and laboratory findings of the patient during the 1st year of follow-up. CONCLUSIONS This is the first case to be reported of Sjögren's syndrome following SIT. Patients undergoing SIT must be carefully followed up for the development of autoimmunity and an autoimmune disease.