Abstract Human fetal spinal cords and other non-neural tissues from cases with gestational age from 6 to 21 weeks were examined with a panel of antibodies to different domains of β-amyloid precursor proteins (β-AMPs). In the early developmental stages, the β-APPs were expressed in three distinct layers, i.e., primitive neuroepithelial cell layer, mantle layer and marginal layer. β-APP immunoreactivity was most prominent in cell bodies of putative neuroblasts located in the outer ventral part of the mantle layer. β-APP expression diminished as the spinal cord matured and a weak residual immunoreactivity was detected exclusively in a subset of the anterior horn cells by 21 weeks gestational age. Throughout the gestational ages examined, no convincing β / A4 immunostaining was seen in any of the spinal cord regions. Outside the spinal cord, β-APP immunostaining was consistently present in (1) cell bodies and proximal nerves of immature neurons of dorsal root ganglia and in (2) myotubules, although these cells were devoid of β / A4 immunoreactivity. Western blot analysis of fetal spinal cord revealed immunoreactive bands with apparant molecular weight between 100 and 140 kDa in the membrane-associated fraction, while soluble proteins with a molecular mass centered on 115 kDa were detected in the cytosolic fraction. Our results indicate that: (1) one or more isoforms of full length β-APPs are expressed at very early gestational ages in the developing human spinal cord; (2) the normal metabolism of β-APPs does not result in accumulations of β / A4 fragments.