The age-related alterations in the plasticity of synaptic energy-requiring ATPases [Na+,K(+)-ATPase, low- and high-affinity Ca(2+)-ATPase, Mg(2+)-ATPase, and Ca2+,Mg(2+)-ATPase] were assayed in synaptosomes and synaptosomal subfractions [namely, synaptosomal plasma membranes and synaptic vesicles] in the cerebral cortex from 3- and 24-month-old normoxic rats and rats subjected to either mild or severe chronic (four weeks) intermittent normobaric hypoxia. With the exception of the high-affinity Ca(2+)-ATPase, aging induced a decrease in the ATPase activities from normoxic rats. The adaptation to mild hypoxia was characterized by an increase in the activity of Mg(2+)-ATPase in 3-month-old rats, concomitant with a decrease in the activities of: (i) Na+,K(+)-ATPase and high-affinity Ca(2+)-ATPase in both 3- and 24-month-old rats, and (ii) Ca2+,Mg(2+)-ATPase in 3-month-old ones. The adaptation to chronic intermittent severe hypoxia was characterized by a decrease in the activities of: (i) Na+,K(+)-ATPase, Ca2+,Mg(2+)-ATPase and high-affinity Ca(2+)-ATPase in both 3- and 24-month-old rats, and (ii) low-affinity Ca(2+)-ATPase only in 24-month-old ones. The effect on Mg(2+)-ATPase activity was characterized by a decrease in the activity of the enzymatic form located in the synaptic plasma membranes [involved in ATP hydrolysis to adenosine production], concomitant with an increase in the activity of the form located in the synaptic vesicles [involved in the turnover of transmitters, e.g., glutamate]