This research protocol was designed to test the effectiveness of a gel containing silicon dioxide, aloe vera, and allantoin in the healing of recurrent aphthous ulcers. The subjects were patients with histories of developing multiple ulcers on the oral mucosa during a 3-to-4-month period. The parameters used to evaluate healing were number of lesions during a 3-to-4-month period, length of the interval between ulcers, size of ulcers, and pain from ulcers. An approach was used in which data were accumulated from diaries maintained by the subjects throughout the study intervals. Because 3 active substances were present in the gel, a preliminary study (study I) was performed to indicate the effect of each active substance and each combination. In this phase, different combinations of the substances were compared with the use of the 23 factorial experimental design. The results of this study demonstrated that statistical differences in the durations of lesions (P = .017) were present when all 3 substances were included in the gel. In the next study (study II), which was initiated to test the results of study I, additional subjects were divided into 2 groups; one used a control gel with silicon dioxide, and the other a gel with all 3 active substances. Study II found no statistical differences in the parameters when the 2 groups were compared. In study III, a modified crossover design was used with the subjects of study II, and a significant difference was found in lesion-free intervals (P = .0335) and length of time for the study (P = .0001). The differences in lesion intervals may have been caused by the differences in study length. Alteration in the occurrence of aphthous ulcers was demonstrated by the reduction in numbers of lesions in study I and by the increase in length of intervals between lesions in study III. However, a consistent pattern was not present; this indicated a lack of effect of the gel on aphthous ulcers.