The effects of aging and diabetes on the uptake and incorporation of [3H]estradiol (E) in various brain areas was analyzed in C57BL/KsJ mice. Control (C; +/?) and diabetic (D; db/db) mice were pulse treated (30 min) with 10 muCi of [3H]E at 1, 2 and 4 months of age and the brains were subsequently microdissected, digested and the amount of incorporated [3H]E assessed. The pituitary and amygdala exhibited the highest levels of [3H]E incorporation of all brain areas, with the hypothalamus, septal nuclei, midbrain, hippocampus, medulla and parietal cortex exhibiting moderate retention levels at one month of age in C animals. All brain areas in D mice had significantly lower incorporation rates than in matchpaired, C animals. An age-related decrease in [3H]E accumulation was observed in all brain regions in both C and D groups, with a significant depression in [3H]E incorporation occurring between 1 and 4 months of age. These data demonstrate that an age-related decrease in [3H]E uptake occurs in most brain areas in the C57BL/KsJ mouse, and that the diabetic condition exacerbates this phenomenon.