This study investigated whether sensitivity of the nocturnal melatonin suppression response to light depends on the area of the retina exposed. The reason to suspect uneven spatial sensitivity distribution stems from animal work that revealed that retinal ganglion cells projecting to the suprachiasmatic nuclei (SCN) are unequally distributed in several species of mammals. Four distinct areas of the retinas of 8 volunteers were selectively exposed to 500 lux between 1:30 a.m. and 3:30 a.m. Saliva samples were taken before, during, and after light exposure in 1-h intervals. A significant difference in sensitivity was found between exposure of the lateral and nasal parts of the retinas, showing that melatonin suppression is maximal on exposure of the nasal part of the retina. The results imply that artificial manipulation of the circadian pacemaker to alleviate jet lag, to improve alertness in shift workers, and possibly to treat patients suffering from seasonal affective disorder should encompass light exposure of the nasal retina.