Lung cancer is one of the leading causes of cancer death in the world and is notoriously difficult to treat effectively. In the present study, male Swiss albino mice were divided into five groups of six animals each: group I animals received corn oil orally and served as a control; group II cancer-induced animals received benzo(a)pyrene (50 mg/kg bodyweight dissolved in corn oil, orally) twice weekly for four successive weeks; group III cancer-bearing animals (after 12 weeks of induction) were treated with paclitaxel (33 mg/kg bodyweight, i.p.) once weekly for 4 weeks; group IV cancer-bearing animals were treated with paclitaxel along with Withania somnifera (400 mg/kg bodyweight) orally once weekly for 4 weeks; and group V animals constituted the drug control treated with paclitaxel along with W. somnifera. The serum, lung and liver were investigated biochemically for aryl hydrocarbon hydroxylase, γ γ γ γ-glutamyl transpeptidase, 5′ ′ ′ ′-nucleotidase, lactate dehydrogenase and proteinbound carbohydrate components (hexose, hexosamine and sialic acid). These enzyme activities were increased significantly in cancer-bearing animals compared with control animals. The elevation of these in cancer-bearing animals was indicative of the persistent deteriorating effect of benzo(a)pyrene in cancerbearing animals. Our data suggest that paclitaxel, administered with W. somnifera, may extend its chemotherapeutic effect through modulating protein-bound carbohydrate levels and marker enzymes, as they are indicators of cancer. The combination of paclitaxel with W. somnifera could effectively treat the benzo(a)pyrene-induced lung cancer in mice by offering protection from reactive oxygen species damage and also by suppressing cell proliferation. (Cancer Sci 2006; 97: 658-664) L ung cancer is a major cause of morbidity and mortality worldwide both in men and women, accounting for 29% of all cancers. The incidence of lung cancer remains very high. The World Health Organization estimates that lung cancer is the most frequent cancer in the world today, and the global incidence of lung cancer is increasing at a rate of 0.5% per year due to the fact that the smoking epidemic continuous to spread to developing countries. Lung cancer is strongly related to smoking. We know that 85-95% of lung cancer patients are smokers. In many developed countries smoking prevalence is approximately the same among women and men.(1) Polycyclic aromatic hydrocarbons (PAH), many of which are carcinogenic, are widespread environmental contaminants produced by incomplete combustion. Mammalian metabolism of carcinogenic PAH mediated by cytochromes P450 and epoxide hydrolase generates, among other metabolites, bay region diol epoxides. The tumorigenic potential of these metabolites most likely results from their reaction with cellular DNA to form miscoding adducts.(2) The radical cationic forms of benzo(a)pyrene (B[a]P) may be involved in both the mechanism and metabolic activation leading to the formation of DNA adducts, which are key components of the tumo...