Two hundred and ninety women who had just given birth were divided into four groups with respect to the smoking habit: OP – women that did not smoke during pregnancy; PP – women that did not smoke during pregnancy but were exposed to passive smoking; AP – women that were active smokers during pregnancy, but their partners or household members were not; KP – women that were active smokers during pregnancy as well as their partners and/or household members. Every woman completed a questionnaire, and placental samples were taken for histopathologicl and immunochemical analysis with p53, bcl-2, HSP-70 and metallothionein. Placental morphological index (MIP), placental immuno-histochemical index (IHIP) and placental intoxication index (IIP) as the sum total of MIP and IHIP were determined. On the basis of neonatological parameters and macroscopic placental features it was not possible to distinguish between newborns and placentas exposed to tobacco smoke and unexposed ones. Placentas exposed to tobacco smoke during gestation could be distinguished by histological and immunohistochemical analysis through MIP, IHIP and IIP: MIP, IHIP and IIP could distinguish unexposed placentas and placentas exposed to harmful influences, while MIP and IIP also distinguish the mode of exposure because of the significantly different values of the parameters that showed a difference between passive and active exposure, but not between active and combined exposure. Accordingly, MIP, IHIP, and IIP can be used as indicators of placental intoxication by tobacco smoke.