The vacuolar change in Golgi complexes known as "honeycomb Golgi" has been described as the ultrastructural hallmark of a specific tumor that has been called the "female gonadotroph" adenoma of the human pituitary. Recently, a few adenomas presenting with Cushing's disease have been reported to exhibit this feature. To clarify the significance of a "honeycomb Golgi" in the classification of pituitary adenomas, we studied clinically nonfunctioning adenomas with or without "honeycomb Golgi" using immunohistochemistry for adenohypophysial hormones and RT-PCR for the cell-specific transcription factors Tpit that identifies corticotrophs and SF-1 that identifies gonadotrophs. All adenomas were from women. Among 20 adenomas with complete "honeycomb Golgi" change, gonadotrophin subunits were totally immunonegative, but ACTH was positive in a few cells of 12 adenomas. Among eight adenomas with partial vacuolar change of the Golgi complex, five were positive for gonadotrophins and two were positive for ACTH. A subgroup of these lesions were examined by RT-PCR and among eight adenomas with typical "honeycomb Golgi" one case expressed both Tpit and SF-1, probably due to contamination with normal pituitary and another expressed neither Tpit nor SF-1. Of the remaining six cases, Tpit was expressed in two cases and SF-1 in four. These findings indicate that "honeycomb Golgi" change can been seen in corticotroph adenomas as well as gonadotroph adenomas. The reason why this vacuolar change occurs only in females remains to be clarified.