Although much less common than before the advent of the antibiotics, cognitive impairment due to general paresis can still be found in clinical practice. Five patients with general paresis underwent longitudinal neuropsychological assessment; on the occasion of the final evaluation, Single Photon Emission Tomography (SPECT) was also performed in four cases. The most frequent cognitive deficit at admission was long term spatial memory impairment, which was present in four patients. Only the two patients who received the highest dosage of intravenous penicillin therapy showed significant improvement at neuropsychological tests after treatment. SPECT findings included areas of cortical hypoperfusion and/or perfusion asymmetry in three out of four patients.