Sodium lauryl sulfate (SLS), the most widely used detergent in toothpastes, has been reported to cause adverse effects on oral soft tissues. This double-blind cross-over study describes the oral mucosal effects of SLS-containing toothpastes and pastes containing a zwitterionic detergent, cocoamidopropyl-betaine (CAPB) in an experimental model in 28 healthy females. Seven toothpastes, differing only in detergent concentration and/or type, were used: SLS (0.5, 1.0, 1.5%), CAPB (0.64, 1.27, 1.90%) and a placebo. Each participant applied 1 cm of assigned test toothpaste via a cap splint to the teeth and the mucosa of the upper jaw. The splints were used twice daily for 2 min during a period of 4 d, after which the participants were examined for oral desquamation. No other oral hygiene was allowed during the test periods. Ten days brushing with a detergent-free toothpaste was performed between each test period. Forty-five desquamative reactions were observed in 21 of 27 subjects (one was excluded) during the trial. Forty-two reactions were recorded during the SLS periods and the remaining three during the CAPB periods. The detergent-free toothpaste did not result in oral desquamation. SLS in toothpastes significantly increased the incidence of desquamation of the oral mucosa compared with toothpastes containing the detergent CAPB. The model used is not directly relevant to normal toothbrushing with toothpaste, but indicates that sensitive patients may contract mucosal irritation through SLS in toothpastes. Less toxic detergents, e.g. CAPB, are desirable in oral hygiene products.