Exocytosis proteins play an important role in the secretory activities of anterior pituitary cells and adenoma cells. An immunohistochemical study was conducted to elucidate the functional significance of these proteins in growth hormone (GH)-producing adenomas. We studied 40 GH-producing adenomas, 10 prolactinomas, and 10 clinically nonfunctioning (NF) adenomas immunohistochemically with antibodies specific for Rab3B and SNAP-25, both of which are considered essential in secretory activities of the pituitary, and keratin 8 (clone CAM5.2). The tumor volume (TV) was estimated with high-resolution magnetic resonance imaging. Immunoreactivity for Rab3B, which was granular in the cytoplasm, varied in GH adenomas, but was negative in prolactinomas and NF adenomas. Reactivity for SNAP-25, which was linear on the plasma membrane, varied in GH adenomas, and was intensely positive in prolactinomas, and negative in NF adenomas. In GH adenomas, an increased percentage of adenoma cells with dot-like immunoreactivity for keratin 8 was associated with decreased reactivities for Rab3B (R=0.739, P < 0.0001) and SNAP-25 (R=0.840, P < 0.0001). Increased reactivity for SNAP-25 correlated positively with plasma GH level per unit TV (R=0.685, P < 0.0001). The immunoreactivities for Rab3B and SNAP-25 may reflect the number of secretory granules and exocytosis activity, respectively, in pituitary adenomas, including GH adenomas.