To assess the effectiveness of bromocriptine in reducing the size of PRL-secreting macroadenomas with extra-sellar extension, we conducted a prospective multicenter trial inpatients without prior radiotherapy, applying a standard protocol of treatment and tumor size evaluation. Basal serum PRL levels [1441 ± 417 (±SEM) ng/ml for women; 3451 ± 1111 ng/ml for men] fell in all patients and to 11% or less of basal values in all patients but 1. Normal PRL levels were reached in 18 of the 27 patients. In 13 patients (46%), tumor size was reduced by greater than 50%, in 5 patients (18%) by about 50%, and in 9 patients (36%) by approximately 10-25%. The extent of tumor size reduction did not correlate with basal PRL, nadir PRL, percent fall in PRL, or whether PRL levels reached normal. However, a reduction in PRL levels always preceded any detectable change intumor size. In 19 patients, reduction in tumor size was evident by 6 weeks, but in the other 8, suchreduction was not noted until the 6 month evaluation. In the 4 patients in whom bromocriptine was discontinued at the end of 1 yr, tumor reexpansion occurred in 3. Visual fields improved in 9 ofhe 10 patients in whom they were abnormal. Because of the excellent results found in most of the patients n i this series, we suggest thattherapy with bromocriptine should be considered as initial management for patients with PRL-secreting macroadenomas. © 1985 by The Endocrine Society.