Sensory neurons can be classified into subpopulations based on a variety of characteristics, including their morphology and physiological modalities. Whether any of these classifications correlates with neurotrophic sensitivities has not been determined. We have recently reported that a subpopulation of large diameter sensory neurons of the rat contain neurotrophin 3-like immunoreactivity (NT3-ir). In this study, we have further characterised NT3-ir sensory neurons by their size, segmental localization, and peripheral projections by combined techniques of retrograde tracing and immunohistochemistry. The size distribution showed that NT3-ir was localised to a subpopulation of large-diameter neurons ranging from 560 to 3,120 microns2. Greater numbers of NT3-ir neurons reside in trigeminal (43% of total), cervical (36%), and lumbar (39%) than in thoracic spinal ganglia (13-17%). In combination with Fluoro-Gold retrograde tracing, it was found that about 30% of sensory neurons projecting to the tibial muscle were NT3-ir, compared with 39% for tendon, 50% for whisker hair follicles, 17% for subdermis or epidermis, and only 1% for kidney or adrenal gland. These studies indicate that NT3-ir sensory neurons mainly project to skin and muscles but not viscera. Thus, the characterization of NT3-ir spinal sensory neurons suggests that large sensory neurons subserving proprioception and mechanoception require NT3 for the maintenance of normal function.