Sequence learning depends on the striatal system, but recent findings also implicate the mediotemporal lobe (MTL) system. Schendan, Searl, Melrose, and Stern (2003) found higher-order associative, learning-related activation in the striatum, dorsolateral prefrontal cortex, and the MTL during the early acquisition phase of both implicit and explicit variants of a serial response time task. This functional MRI (fMRI) study capitalized on this task to determine how changes in MTL function observed in aging and compromised frontostriatal function characteristic of patients with Parkinson's disease (PD) impacts sequence learning and memory under implicit instructions. Brain activity was compared between “sequence” and “random” conditions in 12 nondemented patients with PD and education- and gender-matched healthy control participants of whom 12 were age matched (MC) and 14 were younger (YC). Behaviorally, sequence-specific learning of higher-order associations was reduced with aging and changed further with PD and resulted primarily in implicit knowledge in the older participants. fMRI revealed reduced intensity and extent of sequence learning-related activation in older relative to younger people in frontostriatal circuits and the MTL. This was because signal was greater for the sequence than random condition in younger people, whereas older people, especially those with PD, showed the opposite pattern. Both older groups also showed increased activation to the task itself relative to baseline fixation. In addition, right MTL showed hypoactivation and left MTL hyperactivation in PD relative to the MC group. The results suggest changes in frontostriatal and MTL activity occur during aging that affect task-related activity and the initial acquisition phase of implicit higher-order sequence learning. In addition, the results suggest that Parkinson's disease adversely affects processes in the MTL including sequence learning and memory.