Cyclohexenonic long-chain fatty alcohols constitute a family of synthetic compounds with trophic, secretagogue and antioxidant properties. Despite their multiple biological actions in neuronal and non-neuronal tissues, the intracellular mechanisms underlying CFA activity remain unknown. In the present study, we show that 3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one (tCFA15) directly mobilizes Ca(2+) in the pituitary neural lobe synaptosomes and in primary sensory neurons from dorsal root ganglia. This effect is dependent on the presence of extracellular Ca(2+), but does not involve transmembrane voltage-operated calcium channels. Using a combination of pharmacological agents that block or deplete intracellular Ca(2+) stores, our results suggest the implication of a calcium induced-calcium release mechanism evoked by tCFA15-induced Ca(2+) influx. To our knowledge, these findings constitute the first attempt towards the comprehension of the biological actions of cyclohexenonic long-chain fatty alcohols at a molecular level.