The chemopreventive effect of 5, 10 and 15 p.p.m. (as selenium) of l, 4-phenylenebis(methylene)selenocyanate (p-XSC) on lung tumor induction by the tobacco-specific 4-(methylnitrosamino)-l-(3-pyridyI)-l-butanone (NNK) was examined in female A/J mice by administering p-XSC in the diet. Sodium selenite (5 p.p.m. selenium) was given in the same manner for comparison with p-XSC. Mice were fed experimental diets containing the selenium compounds 1 week before i.p. injection of 10 μunol NNK in 0.1 ml saline and throughout the experiment until termination, 16 weeks after carcinogen administration. Body weights of the mice in the different dietary groups did not differ significantly. p-XSC significantly inhibited lung tumor multiplicity from 7.6 tumors per mouse in the control group to 4.1, 3.3 and 1.8 tumors per mouse in animals given 5, 10 and 15 p.p.m. of selenium respectively. In contrast, 5 p.p.m. sodium selenite had no protective effect against lung tumor induction. The results of this study clearly indicate that the structure of selenium-containing compounds is important in determining their efficacy as chemopreventive agents.