1. The cardiovascular effects of direct microinfusions of clonidine into the nucleus tractus solitarii (NTS) in rats of different ages were studied. 2. Clonidine microinfused into the NTS produced a dose-dependent hypotensive and bradycardic response, which was reduced by previous microinfusion of yohimbine but not of propranolol or prazosin. 3. Unilateral microinfusion of clonidine into the NTS produced a significantly smaller hypotensive and bradycardic response in 16 month old rats than in 3 month old rats, whereas in older animals (24 month old) the same doses of clonidine were ineffective. In 16 month old rats, yohimbine given into the NTS produced a smaller pressor and tachycardic response than in 3 month old rats whereas in 24 month old animals yohimbine, at the same doses, was unable to change blood pressure and heart rate. 4. Oral administration of phosphatidylserine (50 mg kg-1 day-1 for 30 consecutive days) enhanced the hypotensive and bradycardic response to clonidine microinfused into the NTS in 16 month old rats. The same schedule of treatment with phosphatidylserine did not affect the cardiovascular response to clonidine in young (3 month old) rats and did not restore responsiveness to clonidine in older rats (24 month old). 5. Methoxamine and phentolamine, given intravenously, produced similar pressor and depressor responses, respectively in 3, 16 and 24 month old rats, suggesting that the decreased sensitivity to clonidine in old rats was not due to peripheral cardiovascular changes. 6. In conclusion, the present results indicate that, during aging, there is a decreased sensitivity of alpha 2-adrenoceptors in the brain. Such an alteration can be reversed by chronic treatment with phosphatidylserine during the initial but not the later stages of aging.