Constitutively expressed isoforms of nitric oxide synthase in the brain comprise the neuronal (nNOS) and the endothelial (eNOS) enzyme. However, they show striking differences in terms of their preferred histological compartments: nNOS is found predominantly in neurons, eNOS preferentially in endothelia. Our study demonstrates, by means of in-situ hybridization, that nNOS mRNA also localizes to the endothelia of pial vessels but not to those of capillaries. eNOS, however, is expressed in brain capillaries and, as shown by immunohistochemistry, likewise in larger blood vessels, but never in neurons or glia. The endothelial expression of nNOS and eNOS was also confirmed by RT-PCR. The differential distribution of NOS isoforms in brain vessels might be explained with their different mode of activation by stimuli affecting only one particular NOS isoform. (C) 1997 Elsevier Science Ireland Ltd.