The use of Swedish oral moist snuff is a widespread habit in Sweden. In 1999, 25% of the adult male population and 3.1% of the female population were users of snuff. The aim of the present study was to evaluate how variations in pH and nicotine concentrations of snuff affect the oral mucosa, clinically and histologically, salivary pH and daily nicotine intake in 20 habitual users of loose snuff. The subjects were studied during use of their usual brand, after 12 weeks use of a snuff with lower pH and after another 12 weeks use of a snuff with both lower pH and lower nicotine concentration. Consumption data, oral soft tissue changes, salivary pH and nicotine intake were meas-ured. Further, biopsies were taken from the central part of the clinically observed lesions and histological changes were analysed. The subjects maintained their snuff consumption during the observation periods. The average salivary pH was higher during snuff use than in the morning. Further, it was higher shortly after the snuff was removed than during snuff use. After having switched to the snuff with both lower pH and lower nicotine concentrations, they showed a significant reduction in daily nicotine intake and developed significantly less pronounced clinical and histological changes. These results indicate that nicotine is one of the substances in snuff that has a biological effect on the oral mucosa. However, there also seems to be a synergistic effect between the pH and nicotine concentration in the snuff.