Three age groups of male Swiss albino CD-1 mice (2-3 mo, 6-7 mo, and 14-15 mo) were treated with a 120 mg/kg dose of the protein synthesis inhibitor anisomycin or with an equal volume of saline at various times before and after training (20 min pretraining, 0, 10, 30, or 180 min posttraining) in a shock motivated passive-avoidance task. Young (2-3 mo) and intermediate-aged (6-7 mo) mice treated with anisomycin before or immediately after training demonstrated impaired retention at a 7 day test, but retention was normal for mice injected 10, 30 or 180 min posttraining. The older mice (14-15 mo) showed similar results, with one exception: those older mice injected with anisomycin 10 min posttraining were significantly impaired in retention as compared to older saline controls and to identically treated young or intermediate-age mice. The prolonged gradient of retrograde amnesia demonstrated by older mice could not be accounted for by impaired acquisition, impaired short-term memory, altered spontaneous locomotor activity, or differential inhibition of brain protein synthesis.