Stereologic procedures were used to quantitate spontaneously occurring liver foci of altered staining in control Fischer-344 rats at 33, 59, 85, and 111 weeks of age. Foci were identified using hematoxylin and eosin stained sections. In both males and females, foci were first observed at 59 weeks. The number of foci per cubic centimeter of liver, as well as mean focal volume, increased significantly with age. Between 85 and 111 weeks, the number of foci per liver increased 3.5 times in females but was unchanged in males. When three groups of 111-week-old animals were evaluated, females consistently had a greater number of foci per cubic centimeter of liver and mean focal volume than males of the same group. For the three groups evaluated at 111 weeks, the mean number of foci per liver ranged from 431 to 1865 in males and from 727 to 1654 in females. The mean volume fraction (% of the liver) occupied by foci ranged from 0.28 to 1.0% in males and from 1.42 to 4.15% in females. When focal staining characteristics were investigated, the majority of foci were basophilic in both sexes at all time points examined. However, males consistently had a higher percentage of eosinophilic foci than females.