The hypothalamic suprachiasmatic nucleus (SCN) receives afferents from the retina and the midbrain raphe. The retinal innervation mediates photic entrainment of the SCN circadian oscillator whereas the serotonergic input arising from the midbrain raphe nuclei appears to modulate retinohypothalamic neurotransmission. We hypothesized that serotonergic innervation of the SCN may modulate retinal input by activation of 5HT1B presynaptic receptors on retinal axon terminals in the SCN. We tested this hypothesis using the 5HT1B receptor agonist, 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP). Systemic administration of TFMPP prior to light stimulation significantly attenuated light-induced phase shifts of the circadian activity rhythm and Fos expression in the SCN. These results in the mouse support our earlier findings in the hamster [Pickard, G.E., Weber, E.T., Scott, P.A., Riberdy, A.F. and Rea, M.A., J. Neurosci., 16 (1996) 8208-8220] and are consistent with the interpretation that 5HT1B presynaptic receptors participate in the regulation of photic input to the SCN.