Nitric oxide synthase, which generates the physiological messenger mol
ecule nitric oxide, and its associated NADPH diaphorase (NADPHd) activ
ity are distributed throughout selective neuronal populations of the c
entral and peripheral nervous system. Considerable evidence has been a
ccumulated to indicate that NADPHd activity labels cells lacking neuro
nal nitric oxide synthase, i.e., the specificity of the reaction has t
o be considered for the reliable detection of the enzyme in neuronal b
ut also non-neuronal tissue. In the present review, critical aspects o
f nitric oxide synthase visualization in neurones, using its NADPHd ac
tivity, are discussed. Furthermore, the organization of the central an
d peripheral nitric oxide synthase-containing neuronal systems is desc
ribed. Nitric oxide synthase is present in local cortical and striatal
neurones, hypothalamic magnocellular neurones, mesopontine cholinergi
c neurones, cerebellar intemeurones, preganglionic sympathetic and par
asympathetic neurones, neurones in parasympathetic autonomic and enter
ic ganglia and primary viscero-afferent neurones. Finally, injury-rela
ted alterations in nitric oxide synthase activity are briefly outlined
. In this respect, the histochemistry of nitric oxide synthase may rep
resent a valuable marker for neurochemical, if not structural, alterat
ions observed in neural diseases, regeneration and transplantation.