Pre-existing trauma to basal forebrain corticopetal cholinergic neurons has been hypothesized to render this system vulnerable to age-related processes. The present longitudinal study assessed the interactions between the effects of partial cortical cholinergic deafferentation and aging on sustained attention performance. After pre-surgical training, animals were given sham-surgery or bilateral infusions of the immunotoxin 192 IgG-saporin into the basal forebrain. The lesion was intended to yield a limited loss of cortical cholinergic inputs and thus to produce minor immediate effects on sustained attention performance. All animals were tested continuously until age 36 months. The attentional performance of lesioned and sham-lesioned animals did not dissociate until age 31 months, when the lesioned animals exhibited an impairment in overall sustained attention performance. Importantly, this impairment interacted with the effects of time-on-task, and thus reflected a specific impairment in attentional processes. These results support the notion that pre-existing damage to the basal forebrain corticopetal cholinergic neurons yields age-related impairments in the attentional capabilities that depend on the integrity of this neuronal system.