The purpose of this study was to investigate the uptake and metabolism of nicotine by smokeless (oral) tobacco users and to find out if the less pronounced clinical changes in the oral mucosa in users of portion-bag packed oral moist snuff (snus) compared with the changes in the mucosa of loose snus users are correlated to exposure and uptake of tobacco constituents. 54 habitual users of smokeless tobacco were selected for the study: 22 loose snus users, 23 users of portion-bag packed snus and 9 users of chewing tobacco. In accordance with previous findings, less pronounced clinical changes in the oral mucosa were recorded in portion-bag users compared with loose snus users. The clinical findings observed in the oral mucosa of users of chewing tobacco were leukoedema and slight clinical "snus changes". The average intake of nicotine (measured as nicotine equivalents excreted during 24 h) for snus users was 35 mg, and was 50% higher for users of chewing tobacco. The average steady-state saliva cotinine concentration was about 300 ng/ml for both categories of snus users, which is similar to that found in smokers, while the average concentration found in users of chewing tobacco was 50% higher. There was a good correlation between saliva cotinine concentration and the 24 h intake of nicotine. The average excretion profile of nicotine was similar in all three groups of smokeless tobacco users, being on average: nicotine 8%, nicotine-GlcA 3%, cotinine 8%, cotinine-GlcA 9%, 3'-hydroxycotinine 42%, 3'hydroxycotinine-GlcA 19%, nicotine-N'-oxide 9% and cotinine-N-oxide 3%.(ABSTRACT TRUNCATED AT 250 WORDS)