Koltzenburg, Martin, Cheryl L. Stucky, and Gary R. Lewin. Receptive properties of mouse sensory neurons innervating hairy skin. J. Neurophysiol. 78: 1841–1850, 1997. Using an in vitro nerve skin preparation and controlled mechanical or thermal stimuli, we analyzed the receptive properties of 277 mechanosensitive single primary afferents with myelinated (n = 251) or unmyelinated (n = 26) axons innervating the hairy skin in adult or 2-wk-old mice. Afferents were recorded from small filaments of either sural or saphenous nerves in an outbred mice strain or in the inbred Balb/c strain. On the basis of their receptive properties and conduction velocity, several receptor types could be distinguished. In adult animals (>6 wk old), 54% of the large myelinated fibers (Aβ, n = 83) showed rapidly adapting (RA) discharges to constant force stimuli and probably innervated hair follicles, whereas 46% displayed a slowly adapting (SA) response and probably innervated Merkel cells in touch domes. Among thin myelinated fibers (Aδ, n = 91), 34% were sensitive D hair receptors and 66% were high-threshold mechanoreceptors (AM fibers). Unmyelinated fibers had high mechanical thresholds and nociceptive functions. All receptor types had characteristic stimulus-response functions to suprathreshold force stimuli. Noxious heat stimuli (15-s ramp from 32 to 47°C measured at the corium side of the skin) excited 26% (5 of 19) of AM fibers with a threshold of 42.5 ± 1.4°C (mean ± SE) and an average discharge of 15.8 ± 9.7 action potentials and 41% (7 of 17) C fibers with a mean threshold of 37.6 ± 1.9°C and an average discharge of 22.0 ± 6.0 action potentials. Noxious cold stimuli activated 1 of 10 AM fibers and 3 of 10 C fibers. One of 10 C units responded to both heat and cold stimuli. All types of afferent fibers present in adult mice could readily be recognized in mice at postnatal day 14. However, fibers had reduced conduction velocities and the stimulus-response function to mechanical stimuli was more shallow in all fibers except for the D hairs. In juvenile mice, 22% of RA units also displayed an SA response at high stimulus intensities; these units were termed RA/SA units. We conclude that all types of cutaneous afferent fibers are already committed to their phenotype 2 wk after birth but undergo some maturation over the following weeks. This preparation has great potential for the study of transgenic mice with targeted mutations of genes that code factors that are involved in the specification of sensory neuron phenotypes.