The effect of a Trichoderma harzianum enzyme preparation containing mutanase (alpha-1,3 glucan glucanohydrolase) on plaque accumulation and composition and on occurrence of gingivitis was assessed in 20 persons in a double-blind cross-over investigation. The enzyme preparation was administered in chewing gum. Two test periods of 1 week were preceded by scaling and cleansing of the teeth, oral hygiene instruction, and controlled hygiene for at least 3 weeks. Oral hygiene measures were discontinued during the test periods, while the persons chewed six pieces of chewing gum per day, one half using enzyme-containing gum, and the other half using placebo gum. The test periods were identical, only enzyme gum was used instead of placebo, or vice versa. Evaluations of plaque and gingivitis showed that less plaque had accumulated and less gingivitis developed during the enzyme than during the placebo period, but bacteriologic studies of interproximal plaque did not reveal differences that could explain the clinical findings. Treatment with the enzyme preparation caused some local side effects, but no primary skin irritation, delayed hypersensitivity, nor anti-enzyme IgE was detected in any of the persons.