To assess the long term effectiveness of combined sequential surgical and medical therapy in the management of prolactin-secreting pituitary macroadenomas, we followed 21 patients for 46 +/- 6 months (mean +/- SE) after diagnosis (range, 12 to 96 months). All patients underwent operation. Six were also treated with bromocriptine, 7.5 mg/day immediately after operation. A group of 15 patients with tumor sizes similar to those of the first group was followed without medical therapy until signs of regrowth of the neoplasia were evident. No patient of the combined therapy group experienced a recurrence of the disease. On the other hand, only 2 patients of the second group were recurrence-free at the end of follow-up. In the other 13 cases, adjunctive therapy had to be established for clinical and radiological evidence of tumor recurrence 26 +/- 7 months after operation. We conclude that combined sequential surgical and medical therapy may be useful in the management of macroprolactinomas. Our hypothesis must be confirmed by studies that compare patients treated with operation plus bromocriptine with patients treated with bromocriptine alone.