PURPOSE. Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate nonimage-forming visual functions such as pupillary constriction and circadian photoentrainment. Optimizing daytime nonimage-forming photostimulation has health benefits. We aimed to enhance ipRGC excitation using flickering instead of steady light. METHODS. Human subjects were tested with a three-dimensional matrix of flickering 463-nm stimuli: three photon counts (13.7, 14.7 and 15.7 log photons cm(-2)), three duty cycles (12%, 47%, and 93%) and seven flicker frequencies (0.1, 0.25, 0.5, 1, 2, 4, and 7 Hz). Steady-state pupil constrictions were measured. RESULTS. Among stimuli containing 13.7 log photons cm(-2), the one flickering at 2 Hz with a 12% duty cycle evoked the greatest pupil constriction of 48% +/- 4%, 71% greater than that evoked by an equal-intensity (12.3 log photons cm(-2) s(-1)) continuous light. This frequency and duty cycle were also best for 14.7 log photons cm(-2) stimuli, inducing a 58% +/- 4% constriction which was 38% more than that caused by an equal-intensity (13.3 log photons cm(-2) s(-1)) constant light. For 15.7 log photons cm(-2) stimuli, the 1-Hz, 47% duty cycle flicker was optimal although it evoked the same constriction as the best 14.7 log photons cm(-2) flicker. CONCLUSIONS. Pupillary constriction depends on flicker frequency and duty cycle besides intensity. Among the stimuli tested, the one with the lowest photon count inducing a maximal response is 13.3 log photons cm(-2) s(-1) flickering at 2 Hz with 12% duty cycle. Our data could guide the design of healthier architectural lighting and better phototherapy devices for treating seasonal affective disorder and jet lag.