Leydig cells were isolated from the testes of adult young (5--7 months), old (21 months), and senile (27 months) mice using a highly preservative Percoll procedure. The yield in Leydig cells per testis from young animals was slightly lower than from the old age groups. hCG-induced testosterone synthesis proceeded in a linear fashion for at least 5 h in all three groups. The maximal steroidogenic capacity of cells from old animals was identical to that from young adults. There was no significant difference between Leydig cells from young and old mice with respect to hCG-induced cAMP accumulation and protein kinase activation. Determination of hCG concentrations required for half-maximal stimulation of testosterone synthesis and cAMP accumulation showed identical, or even lower, values in the old age groups. The phenomenon may be connected with the significant augmentation with age of the DNA content per cell (polyploidization), possibly acting as a compensatory mechanism of age-induced deficiencies. Detailed kinetic studies of cAMP accumulation, protein kinase activation, protein kinase activation, and steroidogenesis as well as ultrastructural analyses support the findings of unimpaired or increased capacities of the testosterone-forming cells in old animals. Thus, the aging of Leydig cells appears to differ from that of other tissues of the mouse (e.g. skeletal muscle), which exhibit decreasing abilities to respond to stimuli.