The present report describes the activity of NADPH-diaphorase (NADPHd) in area 17 of autopsied normal human visual cortex. Four human brains from autopsy tissue (4-8 h postmortem) were fixed by immersion in 4% paraformaldehyde in 0.1 M sodium phosphate buffer, pH 7.2-7.4, or in 10% formalin for 24 h. NADPHd histochemistry was done using the malic enzyme indirect method. The neuropile pattern of enzyme activity presented a clear six-layer appearance. Cell morphology and the laminar distribution of 73 NADPHd-positive neurons are described. All neurons found in area 17 of human cortex were sparsely spiny or smooth cells, located in all cortical layers except layer 4c. Quantitative analysis of the branching pattern of the dendritic tree was carried out. A symmetrical pattern was observed with no particular dendritic bias except for a few white matter and layer 1 cells. Larger dendritic fields were found in white matter cells when compared to the other cortical layers. Comparison of cell densities for gray and white matters showed that 85% of the NADPHd-positive neurons were located in the white matter. NADPHd was colocalized with nitric oxide synthase which produces nitric oxide, a short-life neuromediator implicated in synaptic plasticity, neuroprotection, and neurotoxicity. Thus, the spatial distribution of the NADPHd cells is important for posterior functional studies of the neuromediators in the brain.