We have utilized two distinct monospecific antibodies against the type II (macrophage or inducible) nitric oxide synthase (NOS) isoform to localize the distribution of the enzyme within the human placenta in tissues from normotensive pregnancies and those complicated by pre-eclampsia and/or intrauterine growth restriction. Both antibodies immunolocalize to cells in the villous stroma on frozen sections of villous tissue. Colocalization studies with anti-CD14 or anti-CD45 antibodies that recognize cells of leucocyte or monocyte/macrophage lineage indicate that Hofbauer cells are expressing type II NOS. This is in contrast to expression of type III (endothelial) NOS which is seen in syncytiotrophoblast and in villous vascular endothelium. In some, but not all, normotensive and pathologic placental tissue, some type II NOS immunostaining could be seen in syncytiotrophoblast and vascular endothelium; however, no differences could be discerned between groups of tissues. Expression of type II NOS by Hofbauer cells may indicate they are involved in surveillance against maternal immune insult or maternal pathogens whereby they secrete nitric oxide to exert a cytostatic/cytotoxic effect.