Components of cigarette smoke such as cadmium and polycyclic aromatic hydrocarbons have been shown to induce quinone reductase (QR) activity in placental explants. This study examines the relationship of maternal smoking habit and maternal plasma cotinine concentration with the activities in vitro of both QR and the cytochrome P450 (CYP1A) marker ethoxyresorufin O-deethylase (EROD) in placental tissue. Maternal plasma samples were taken at Week 34 of gestation, and placental tissues were obtained at term. Plasma cotinine concentrations were determined by high-performance liquid chromatography. Trophoblast cytosolic QR and microsomal EROD activities were measured by resazurin reduction and ethoxyresorufin O-dealkylation respectively. QR activity was inhibited 70% by a mixture of dicoumarol (1 microM) and rutin (20 microM). Plasma cotinine concentrations correlated significantly (P < 0.001) with both declared smoking rate (r = 0.67, N = 37) and placental EROD activity (r = 0.63, N = 36), but not with QR activity, whether measured as total QR activity or specifically as either DT-diaphorase or carbonyl reductase. It is concluded that smoking up to 40 cigarettes per day induces EROD but does not affect QR activity in the placenta at term.