All-trans-4-oxo-retinol, a metabolite of retinol synthesized in mouse embryonal carcinoma F9 cells, is active in inducing differentiation of these cells. It also functions as a ligand of retinoic acid receptors and a transcriptional activator of reporter genes. These findings may dispel the notion that retinoic acids are the only transactivators of retinoid receptor-dependent pathways. However, there are weaknesses that need to be addressed in order to confirm the relevance of this retinol-mediated signaling pathway.