Primary progressive aphasia (PPA) is characterized by progressive loss of language, unassociated with generalized cognitive loss and with no uniform pathological abnormality. To address whether the issue of PPA is associated with synaptic loss, we compared immunoreactivity in Broca’s area with that in the adjacent gyrus from a case of progressive, nonfluent PPA using antibodies against synaptophysin. Using semiautomated methods, we assessed serial 0.10 mm2 diameter areas from the cortical surface to the white matter in both the case and the control. In PPA, synaptophysin immunoreactivity was significantly less in Broca’s area than in the adjacent area (optical densities of 0.16 and 0.24). The reduced synaptophysin immunoreactivity was significantly greater in the upper cortex than in the regions of cortex adjacent to the white matter (mean optical densities of 0.14 and 0.18). These data suggest that synaptic loss may be a factor underlying the language deficits in PPA.