The aim of the present clinical double-blind crossover study was to investigate the effect of two different toothpaste detergents, sodium lauryl sulfate (SLS) and cocoamidopropyl betaine (CAPB), as compared with a detergent-free paste, on 30 patients with frequent occurrences of recurrent aphthous ulcers. The study consisted of three 6-week periods during which the patients brushed twice daily with the different test toothpastes. The localization and number of new ulcers were assessed. A significantly higher frequency of aphthous ulcers was demonstrated when the patients brushed with an SLS- than with a CAPB-containing or a detergent-free placebo paste. An SLS-free toothpaste may thus be recommended for patients with recurrent aphthous ulcers.