The endocrinological outcome in four patients with pituitary macroadenomas laterally invading the cavernous sinus, who were treated surgically by the transcranial transcavernous approach, was compared with that in four patients with macroadenomas that had been removed transsphenoidally. The decrease in the elevated serum levels of anterior pituitary hormones after transcavernous surgery ranged from 58.4% to 90.1%, whereas after transsphenoidal surgery it ranged from 0% to 46.1%. The responsiveness of pituitary hormones to stimulation tests was restored and maintained after transcranial transcavernous surgery. Transsphenoidal surgery achieved neither sufficient tumor reduction nor produced a satisfactory endocrinological remission. When cavernous sinus invasion is suspected by magnetic resonance imaging, even if it cannot be confirmed with certainty, transcranial transcavernous surgery is recommended. It is a useful surgical procedure for obtaining a sufficient degree of tumor extirpation and satisfactory endocrinological improvement in patients with macroadenomas laterally invading the cavernous sinus, particularly somatotroph or corticotroph macroadenomas. Postoperatively, mild cranial nerve paresis may occur, but this may resolve in 1-4 months.