Transsphenoidal surgery is the first therapeutic option in acromegaly, but the management of persistent or recurrent cases of the disease after surgery has been controversial. This study presented the results of secondary transnasal surgery for residual or recurring growth hormone (GH)-secreting macroadenoma with reference to intraoperative GH measurement. It focused on 22 patients who underwent secondary transsphenoidal surgery for 18 residual and 4 recurring GH-secreting pituitary macroadenomas from 1990 to 1999. To assess complete tumor removal, plasma GH concentration was measured intraoperatively. Before secondary surgery, plasma GH levels without medical treatment ranged from 2.0 to 239.0 μg/l (mean 31.5 +/– 50.4). Magnetic resonance imaging demonstrated 16 transnasally resectable tumors and 6 nonresectable grossly invasive tumors. Intraoperative plasma GH concentrations declined sufficiently in 9 of 16 with transnasally resectable tumors, but in the remaining 7 cases the tumors were further explored and normalization of GH levels was ultimately obtained in 4 out of these cases. It was impossible to completely remove the tumors in all the 6 patients with transnasally nonresectable tumors. Thirteen of 22 patients achieved endocrinological remission by rigorous criteria. In transnasally resectable tumors, the endocrinological remission rate was 81.3% (13 of 16 patients) with no recurrence during the follow-up period of at least 4 years. Secondary transnasal surgery for residual or recurring GH-secreting pituitary macroadenomas is a safe and effective treatment, if done along with intraoperative GH measurement. Endocrinological remission can be obtained with high probability in patients who suffer from macroadenomas with suprasellar extension, with the exception of transnasally nonresectable grossly invasive tumors.