The efficacy of a protease preparation (Alcalase®, Novo, Denmark) in preventing accumulation of plaque on the fitting surface of complete upper dentures was examined in a double-blind study. Seventeen denture wearers with clinically healthy oral mucosae participated in the study. The protease was dispensed in dissolvent tablets containing 15, 30, 60, 100, 300, 500, or 1000 mg of the enzyme. Enzyme tablets or placebo tablets were dissolved in 150 ml water at 50°C, and the dentures were soaked once daily for 15 min. Denture soaking was performed with or without brushing. The study consisted of 14 1-week periods. At the start of each period the dentures were cleaned by brushing until they showed no visible plaque after staining. At the end of each period plaque was stained and the dentures were photographed. The photographs were projected, and the percentage area of the fitting surface showing plaque deposits was scored with 10% intervals. Statistical analysis showed that there was a significant reduction of plaque scores with increasing enzyme concentration. The most marked reduction in plaque formation was seen when mechanical cleansing was combined with immersion in a 500-mg enzyme solution. At a concentration of 300 mg (or more) the enzyme immersion was as efficient as mechanical cleansing in preventing denture plaque accumulation.