During development, many neurons in the dorsal root ganglia require neurotrophin-3 for survival. However, it is not known precisely which subpopulations of sensory neurons, other than the proprioceptive afferents, are neurotrophin-3 dependent in vivo. In this study, using a battery of neurochemical markers that label different subpopulations of dorsal root ganglion neurons, we found a widespread, about 60-65% loss of cells in most subpopulations in neurotrophin-3 deficient mice. Intermediate losses were found in the heterozygous mutant mice consistent with a gene dosage effect. In agreement with this, the cell size distribution between the homozygous mutant and wild type mice was virtually identical. The loss of small neurons containing calcitonin gene-related peptide, substance P and thiamine monophosphatase activity suggests that many unmyelinated primary afferents are also lost in the mutant animals. The fact that many different sensory neuron subpopulations are lost to the same extent in neurotrophin-3 deficient mice is consistent with the proposed early role of neurotrophin-3 during neurogenesis. Interestingly, calretinin immunoreactive neurons, which contribute a minor subpopulation, were not affected suggesting that neurotrophin-3 independent regulation of neurogenesis occurs in addition to prominent neurotrophin-3 dependent mechanisms.