The risk for oral mucosal lesions associated with use of smokeless tobacco among 1,109 professional baseball players during spring training in 1988 was investigated. Leukoplakia was very strongly associated with use of smokeless tobacco in this population of healthy young men. Of the 423 current smokeless tobacco users, 196 had leukoplakia compared to seven of the 493 nonusers (OR = 60.0, 95% CI = 40.5-88.8). The amount of smokeless tobacco used (in hours per day that smokeless tobacco was held in the mouth), recency of smokeless tobacco use (hours since last use), type (snuff versus chewing tobacco), and brand of snuff used were significantly associated with risk for leukoplakic lesions among smokeless tobacco users. Ninety-eight leukoplakic areas in 92 subjects were biopsied and examined microscopically. All lesions were benign, but one specimen had mild epithelial dysplasia. The long-term significance of leukoplakia in smokeless tobacco users and their relation to oral cancer is not clear.