Mental rotation performance may be used as an index of mental slowing or bradyphrenia and may reflect speed of motor preparation. Previous studies suggest that major depressive disorder (MDD) presents correlates of impaired behavioral performance for mental rotation and psychomotor disturbance. Very little is known about the electrophysiological mechanism underlying this deficit. The present study was the first to investigate the event-related brain potential (ERP) correlates of mental rotation and their mental slowing or bradyphrenia in MDD. ERPs were recorded while we tested 25 MDD patients and 26 healthy controls by evaluating the performance of MDD patients on hand and letter rotation tasks at different orientations, and their 400-to-600-msec time window was measured and analyzed for latencies and peak amplitudes over the electrodes. First, individuals with MDD were slower and made more errors in mentally rotating hands and letters than healthy controls did, and individuals with MDD exhibited a greater difference in response times and errors than controls did between hands and letters. Second, the mean peak amplitude was significantly lower and the mean latency was significantly longer in the 400-to-600-msec time window at the parietal site in the hand tasks in MDD patients than in controls, but this was not seen in the letter task, with only lower mean peak amplitude. MDD patients present the absence of a typical mental rotation function for the amplitude of the rotation-related negativity in the hand and letter tasks. Third, the scalp activity maps in MDD patients exhibited the absence of activation in the left parietal site for the mental rotation of hands, as shown in healthy participants. In contrast, their brain activation for the letter task was similar to those of healthy participants. These data suggest that mental imagery of hands and letters relies on different cognitive and neural mechanisms and indicate that the left posterior parietal lobe is a necessary structure for mental transformations of human hands. Importantly, MDD deficits were more seriously present specific to the hands than the letters. Such impairment may also be an important and possibly defining marker of MDD in particular.