Rab3B, a member of the Rab family is a low molecular weight GTP-binding protein that has been implicated in the regulation of exocytosis. To shed light on its presence in the normal human pituitary and in adenomas, a detailed immunohistochemical study of 130 surgically removed human pituitary adenomas was undertaken, including 23 somatotroph, 32 lactotroph, 19 functional corticotroph, 10 silent subtype 1 and 8 silent subtype 2 corticotroph adenomas, 12 gonadotroph hormone producing, 10 thyrotroph, 7 silent subtype 3 adenomas, and 9 null cell adenomas, 5 of the latter being of oncocytic type. Among the 32 prolactin lactotroph adenomas, 10 had been treated preoperatively with bromocriptine, a dopamine agonist. Among the 23 somatotroph adenomas, 10 were pretreated with octreotide, a long acting somatostatin analog. In addition, 10 nontumorous adenohypophyses were also examined. As used by the World Health Organization, the tumors were classified on the basis of their histologic, immunohistochemical, and ultrastructural characteristics. The results showed Rab3B immunopositivity to be strongest in corticotroph adenomas followed by thyrotroph, lactotroph, gonadotroph, null cell, and somatotroph adenomas. No difference was noted between endocrinologically active and silent corticotroph adenomas. Bromocriptine therapy was associated with decreased Rab3B immunoexpression, whereas pretreatment with octreotide induced no significant reduction. Immunopositivity was cytoplasmic and was evenly distributed. No staining was noted in normal adenohypophyses. Our results add new information to the view that Rab3B is involved in the regulation of pituitary hormone secretion.