Changes in the neuronal content of neurofilament proteins occur in some neuropathological conditions, but little is known about the molecular mechanisms that control both the cell type specificity and the levels of expression of neurofilament genes. In addition to TATA and Sp1 elements, we report here the presence in the neurofilament light (NF-L) promoter region of other regulatory elements, namely, an AP-1 element TGCGTCAG, a Krox-24 element GCACCCCGC, and an Ets-like element AGCAAGCAGGAATTT. These elements constitute binding sites for specific nuclear factors present in aggregated P19 embryonal carcinoma cells. Using cotransfection assays in P19 embryonal carcinoma cells, we show that NF-L promoter fragments fused to the reporter chloramphenicol acetyltransferase gene can be trans-activated by expression vectors encoding FOS and JUN (AP-1) and by Krox-24 protein. The finding of functional elements for immediate early gene products in the NF-L promoter suggests molecular pathways by which the modulation of neurofilament expression can be coupled to growth factors and other external stimuli.