Spontaneous pituitary changes with aging were studied in 130 male Lobund-Wistar rats by light and electron microscopy and immunohistochemistry. These 69 healthy rats (6, 18, and 30 months) and 61 moribund rats (17-50 months) had been maintained in four different groups with the following environmental conditions: conventional full fed, convention food restricted, germ free-full fed, and germ free-food restricted. Gonadotroph nodules were the most frequent proliferative lesions (27 rats). It was difficult to determine whether these nodules were hyperplastic or neoplastic. They were found in aging rats (26 months or older) and their development was delayed by food restriction and germ-free status parallel to prolongation of life-span. No significant difference in incidence of gonadotroph nodules was demonstrated among the four groups. Six lactotroph adenomas, a thyrotroph nodule, and a mixed thyrotroph and lactotroph nodule were also noted in aging rats (30 months or older). In extranodular adenohypophyses, variable numbers of hyperactive gonadotrophs histologically similar to those in gonadotroph nodules were observed in almost all rats including 6-month rats, suggesting that gonadotrophs were continuously hyperactive during their lifetime from an early stage. The mechanism accounting for the development of gonadotroph nodules remain to be established. It can be concluded that food restriction and germ-free status may have a retarding effect but no preventative role in the development of gonadotroph nodules, which are the most common age-associated pituitary lesions of male Lobund-Wistar rats.