Criteria for the non-invasive diagnosis of lymphocytic hypophysitis (LyHy) and the results of the first prospective trial of high dose methylprednisolone pulse therapy (HDMPT) in nine patients are presented. In three patients, the diagnosis was established histologically, and in the others by clinical and endocrinological assessment, MRI, CSF examination, and measurement of thyroglobulin autoantibody concentration. After HDMPT, adenopituitary function improved in four of the nine patients and diabetes insipidus ceased or improved in all four concerned patients. The MRI findings improved in seven patients. LyHy has to be considered in the differential diagnosis of sellar lesions. The presumptive non-invasive diagnosis of LyHy seems possible in a high proportion of patients. HDMPT may result in the improvement of clinical, endocrinological, and MRI findings.