The authors observed the clinical course of 24 women with surgically removed prolactinomas for a mean postoperative interval of 62 months. The frequency of late tumor recurrence and probable factors responsible for the recurrence were investigated. Hyperprolactinemia recurred in 4 of 13 patients with microadenomas (31%) 3 to 9 months after removal. In the macroadenoma group, relapse of hyperprolactinemia occurred in 10 of 11 patients (91%), an average of 26 months after the initial postoperative return to normal prolactin levels. Return of hyperprolactinemia was accompanied by radiologic evidence of tumor recurrence in all patients with macroadenoma, and in one patient with microadenoma. Of 12 tumors in which adjacent dura was available for histopathologic examination, 7 showed dural invasion. Although these seven patients had significantly higher preoperative levels of serum prolactin than the five without dural invasion, there was no significant relation between dural involvement and tumor recurrence. The probabilities of tumor recurring from multifocal adenoma or paraadenomatous lactotrope hyperplasia could not be assessed using our surgical material. The most plausible reason for the high recurrence rate of prolactinomas after apparent surgical cure, in the absence of defined anatomic abnormalities within the pituitary, is a functional abnormality of hypothalamic-pituitary control resulting from a primary hypothalamic disorder.