Cold sensing in mammals is heterogeneous and more than one type of receptor molecule is likely to be involved in the transduction process. Most features of innocuous cold receptors have been explained by TRPM8, the cold and menthol receptor, but their fast adaptation to cooling has not yet been reproduced in cellular systems. In this study we have used a newly developed system for applying fast thermal stimuli to dissociated dorsal root ganglia (DRG) neurons from young rats (150-200 g) in primary culture. We describe a novel type of cold-sensitive rat DRG neuron with rapid adaptation to cooling. These cells (4.3% of the total DRG population) do not express either TRPM8 or the other cold-activated TRP channel, TRPA1, and the epithelial sodium channel (ENaC) is not involved in their transduction. Increases in intracellular calcium induced by cooling in rapidly adapting neurons are caused by calcium entry. These neurons express a large and rapidly adapting cold-induced inward current with a time constant of adaptation in the seconds range, and may correspond to the rapidly adapting cold receptors described in vivo.