Hydrolysis of phosphatidyl inositides (PI) was measured in response to alpha-1-adrenergic agonist in slices of liver prepared from F-344 female rats aged 6-, 15- and 25 months. Tissue was labeled with [H-3]inositol and release of inositol phosphates was measured following a 60-min incubation with a range of concentrations of l-epinephrine. The response to epinephrine was completely blocked by prazosin, indicating the involvement of alpha-1-adrenergic receptors. The maximum response to epinephrine represented release of 13-15% of radioactivity incorporated into the pool of cellular lipids and was unchanged with age. The concentration of epinephrine required for half-maximal stimulation was 1-1.5 mu-M and was also unchanged with age. These data suggest that, although senescence is accompanied by alterations with age in the liver alpha-1-receptor, alpha-1-stimulation of PI hydrolysis is unchanged.