Charcoal (CC) filters of cigarettes are known to significantly reduce a series of volatile constituents in mainstream smoke, including reactive alpha,beta-unsaturated aldehydes such as acrolein and crotonaldehyde. We performed a randomized, crossover, 2-wk brand-switching study with 39 smokers. Twenty of the subjects smoked cellulose acetate (CA) filter tipped cigarettes during wk 1 of the study; the remaining 19 subjects smoked CC filter tipped cigarettes during wk 1. In wk 2, the subjects switched to the corresponding brand with the other filter type, with similar smoking machine-derived tar and nicotine yields. Daily cigarette consumption, carbon monoxide in exhaled breath, salivary cotinine, and urinary nicotine equivalents (molar sum of nicotine plus five major metabolites) did not change significantly when switching to the cigarettes with the other filter type. Urinary excretion rates of 3-hydroxy-1-methylpropylmercapturic acid (metabolite of crotonaldehyde), monohydroxybutenylmercapturic acid (metabolite of 1,3-butadiene), and S-phenylmercapturic acid (metabolite of benzene) were significantly lower when smoking CC compared to CA filter tipped cigarettes. The reduction in amount of 3-hydroxypropylmercapturic acid (metabolite of acrolein) was of borderline significance. Other mercapturic acids and thioethers (the latter is a summary parameter that indicates the exposure to electrophilic compounds) were not or were only slightly reduced upon smoking CC filter tipped cigarettes. We conclude that smoking CC filter tipped cigarettes does not change the uptake of carbon monoxide and nicotine when compared to CA filter tipped cigarettes with similar tar and nicotine yields, but significantly reduces the exposure to toxicologically relevant smoke constituents such as acrolein, crotonaldehyde, 1,3-butadiene, and benzene.