Endostatin, a cleaved fragment of collagen XVIII, is a potent endogenous angiogenesis inhibitor. Elevated serum endostatin levels have been recently reported in patients with various types of neoplasms. The purpose of our study was to evaluate serum concentrations of endostatin in patients harbouring various pituitary adenoma types and to examine the relationship of serum endostatin levels to circulating vascular endothelial growth factor (VEGF) levels. Preoperative serum endostatin and VEGF concentrations were measured using competitive enzyme immunoassays in 71 patients with pituitary adenomas (20 somatotropinomas, 3 corticotropinomas, 6 prolactinomas and 42 clinically nonfunctioning pituitary adenomas - CNFPAs) and compared with levels from age-matched controls. In 35 patients postoperative immunohistochemical investigations were performed. Serum endostatin concentrations were significantly higher in all pituitary adenoma types, except for prolactinomas (somatotropinomas: 124 +/- 16; p < 0.02, corticotropinomas: 157 +/- 42; p < 0.02, prolactinomas: 141 +/- 37; p > 0.05, CNFPAs: 169 +/- 11 ng/ml; p < 0.000005 vs 73 +/- 10 ng/ml in controls). There was a significant positive correlation between endostatin and VEGF serum levels in patients with pituitary adenomas (r = +0.322; p = 0.006). In the control group a significant negative correlation xbetween circulating endostatin and VEGF was found (r = -0.653; p = 0.00975). The simultaneous elevation of endostatin and VEGF may attenuate the pro-angiogenic action of VEGF and be responsible for rather weak neovascularization of pituitary adenomas. Prospective studies are required to assess the usefulness of circulating endostatin and VEGF as markers of progression or recurrence of pituitary tumors.