Neurotrophin-3 (NT-3) exerts its trophic effects in brain via tyrosine kinase receptor C (trkC) signaling. TrkC splice variants produce receptors with (full-length) and without (truncated) a tyrosine kinase domain. The relative abundance of trkC isoforms and the anatomical localization of trkC in the human prefrontal cortex (PFC) in relationship to development and maturation are currently unknown. We have examined the temporo-spatial expression of trkC protein and mRNA during the development of the human PFC. We have found two major isoforms, a full-length (150 kDa) and a truncated (50 kDa) form of the trkC protein in the human PFC. We report that the full-length form is expressed at low levels throughout development while the truncated form is expressed at moderate levels early in development and increases to reach mature levels by adolescence. In contrast, trkC mRNA levels are uniformly expressed throughout most of postnatal life, but decline in ageing. TrkC protein and mRNA are expressed in both pyramidal and non-pyramidal neurons; additionally, trkC protein is detected in glia and neuropil. Our results suggest that truncated trkC is prevalent in the human PFC and that neurons and glia may be responsive to NT-3 in the PFC throughout life.