Signalling via the p42/44 mitogen-activated protein kinase (MAPK) pathway has been identified as an intermediate event coupling light to entrainment of the mammalian circadian clock located in the suprachiasmatic nucleus (SCN). Given this observation, it was of interest to determine where within the entrainment process the MAPK pathway was functioning. In this study, we examined the role of the MAPK pathway as a regulator of light-induced gene expression in the SCN. Towards this end, we characterized the effect pharmacological disruption of the MAPK cascade has on the expression of the immediate-early genes c-Fos, JunB and EGR-1. We report that uncoupling light from MAPK pathway activation attenuated the expression of all three gene products. In the absence of photic stimulation, inhibition of the MAPK pathway did not alter basal gene product expression levels. Light-induced activation of cAMP response element (CRE)-dependent transcription, as assessed using a CRE-LacZ transgenic mouse strain, was also disrupted by blocking MAPK pathway activation. These results reveal that the MAPK cascade functions as one of the first transduction steps leading from light to rapid transcriptional activation, an essential event in the entrainment process. MAPK pathway-dependent gene expression in the SCN may result, in part, from stimulation of CRE-dependent transcription.