The purpose of the present study was to define the clinical and pathological significance of nitric oxide synthase (NOS) in human pituitary adenomas, and to compare these values with those of the MIB-1 labeling index (LI) using an immunohistochemical method. Tissue specimens from 82 cases of surgically-treated pituitary adenomas were immunostained for hormone production for the MIB-1 LI and for the three NOS isoenzymes and five normal pituitary glands were immunostained for the three NOS isoenzymes as a control. The correlation between the clinical variables (age, functional status, tumor size, Hardy's grading, cavernous and/or sphenoid invasiveness, and progression) and mean MIB-1 LI, or between the same clinical variables and NOS immunoreactivity (IR) were analyzed. There was a statistically significant difference in the MIB-1 LI between macroadenomas and microadenomas, and between invasive adenomas and noninvasive adenomas. On the other hand, there was a statistically significant difference in the inducible NOS (iNOS) IR between invasive adenomas and noninvasive adenomas. Furthermore, the iNOS IR had a significant correlation with the MIB-1 LI. Invasive adenomas have a higher iNOS IR, and this correlated with the MIB-1 LI. These findings may be due to the function of iNOS, which plays an important role in tissue injury and repair.