Objective: Several reports have described antipituitary antibodies by immunofluorescent or immunoblotting methods in patients with lymphocytic hypophysitis. However, with the exception of the pituitary hormones, individual antigens specific for the pituitary gland have not been studied. To understand the pathogenesis of lymphocytic hypophysitis and to diagnose this disease efficiently, we studied the presence of autoantibodies against three pituitary-specific proteins, GH and two novel pituitary-specific proteins, namely, pituitary gland specific factor 1a (PGSF1a) and PGSF2. Design: Seventeen patients with lymphocytic hypophysitis, all of whom had pituitary enlargement (5 with lymphocytic adenohypophysitis and 12 with lymphocytic infundibuloneurohypophysitis, including 3 of the latter group proven by biopsy), and 14 patients with hypopituitarism without pituitary enlargement (10 with isolated ACTH deficiency and 4 with idiopathic TSH deficiency) were studied, and compared with 11 patients with non-functioning pituitary macroadenoma, 31 patients with other autoimmune diseases, and 36 healthy controls. Methods: The presence of each antibody was studied by radioligand assay using recombinant human 35 S-labeled protein.Results: Three (18%) patients with lymphocytic hypophysitis having pituitary enlargement, five (36%) patients with hypopituitarism without pituitary enlargement and three (9.7%) patients with other autoimmune diseases were positive for one or more of the antibodies studied. Conclusions: Anti-human GH, anti-PGSF1a, and anti-PGSF2 antibodies were detected in patients with lymphocytic hypophysitis and other hypopituitarism, but were not detected in patients with non-functioning pituitary macroadenoma. Detection of these antibodies may be useful for the diagnosis of lymphocytic hypophysitis.