It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0-I-6.8 mg/day for 12+3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 rain after oral glucose load increased from 5.05_+0.61 to 5.77+0.78 mmol/1 and from 5.61 __ 2.05 to 7.55 +_ 3.05 mmol/1, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin Ale was not observed. Bromocriptine led to a significant decrease in basal as well as glucosestimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients. Similarly to the increased growth hormone secretion after drug withdrawal in 11 patients, a rise in glucose-stimulated insulin secretion was found in all patients; hereby, the mean insulin levels at 0 and 120 min during oral glucose load rose significantly from 7.5+2.6 to 12.1 _+5.1 mU/1 (P<0.01) and from 71.3___52.1 to 101.4_ 50.7mU/1 (P<0.02), respectively.