The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that receives a dense serotonergic innervation from the median raphe nucleus. Serotonin (5-HT) modulates the effects of light on circadian behavior by acting on 5-HT1B receptors on retinohypothalamic (RHT) terminals in the SCN. Activation of 5-HT1B presynaptic receptors on RHT terminals inhibits glutamate release. However, 5-HT1B receptor knockout (5-HT1B KO) mice have attenuated behavioral responses to light [P.J. Sollars, M.D. Ogilvie, A.M. Simpson, G.E. Pickard, Photic entrainment is altered in the 5-HT1B receptor knockout mouse, J. Biol. Rhythms 21 (2006) 21-32]. To assess the cellular response of the 5-HT1B KO SCN to light, light-induced Fos expression was analyzed in 5-HT1B KO and wild-type (WT) mice. In addition, the distribution of melanopsin containing retinal ganglion cells that contribute the majority of axons to the RHT was examined in 5-HT1B KO mice and compared to that of WT mice. Light-induced Fos expression in the SCN was reduced in 5-HT1B KO mice compared to WT mice at circadian time (CT) 16 and CT 23 in a manner similar to the reduction previously described in light-induced behavioral phase shifts. The number of melanopsin retinal ganglion cells was similar in WT and 5-HT1B KO mice. These data taken together with previous data suggest that functional removal of the 5-HT1B receptor results in reduced functional light input to the SCN.