The aim of this study was to test if the three cone photopic visual system is the primary ocular photoreceptor input for human circadian regulation by determining the effects of different wavelengths on light-induced melatonin suppression. Healthy subjects with stable sleeping patterns (wake-up time 7:30 AM +/- 12 min) and normal color vision were exposed at night to full-field 505 nm or 555 nm monochromatic stimuli or darkness for 90 min. Plasma collected before and after exposures was quantified for melatonin. Subjects exposed to 10 irradiances at 505 nm showed no significant differences across mean pre-exposure melatonin values (F=0.505). A sigmoidal fluence-response curve fitted to the melatonin suppression data (R(2)=0.97) indicated that 9.34 x 10(12) photons/cm(2)/sec induced a half-saturation response (ED(50)) while 6.84 x 10(13) photons/cm(2)/sec induced a saturation melatonin suppression response. Further, a dose of 4.19 x 10(13) photon/cm(2)/sec at 505 nm was significantly stronger (P < 0.01) than an equal photon dose at 555 nm for melatonin suppression. These data demonstrate that the cone system that mediates human photopic vision is not the primary photoreceptor system to tranduce light stimuli for melatonin regulation.