Although an in vitro study has hypothesized that expression of ICAM-1 by villous trophoblasts could be important for the influx of maternal immune cells in villitis, it remains to be shown whether the same phenomenon occurs in human villitis. To investigate the expression of ICAM-1 by villous trophoblasts, its relationship with rupture of the trophoblastic barrier and influx of immune cells into the villi, we analysed 18 paraffin-embedded placentas with placentitis (5 by Toxoplasma gondii, 3 by Trypanosoma cruzi, 2 by Paracoccidioides brasiliensis and 8 of unknown aetiology - VUE) and 8 control placentas for detection of ICAM-1 by Immunohistochemistry. All cases but one of placentitis showed trophoblast overexpression of ICAM-1 in the inflamed villi, located almost exclusively next to the areas of trophoblastic rupture. The villitis cases (caused by T cruzi, T gondii and VUE) presented leukocyte adherence in the areas of trophoblastic rupture. When the inflammatory reaction was situated in the intervillous space (placentitis by P brasiliensis), in spite of the trophoblastic rupture and ICAM-1 overexpression there was no leukocyte influx into villi. None of the control placentas showed ICAM-I expression by the trophoblast. We concluded that overexpression. of ICAM-1 by villous trophoblasts occurs during placentitis characterized by accumulation of leukocytes in the villous or intervillous space and probably plays an important role in the rupture of the trophoblastic barrier. The influx of immune cells into the villi appears to be mediated by ICAM-1 but the location of the antigen within villous stroma is certainly a crucial factor for its occurrence. Placenta (2006), 27, 750-757 (c) 2005 Published by Elsevier Ltd.2741826750757