Changes in oral Streptococcus mutans populations were recorded in conjunction with a one-year clinical trial of the anticaries activity of topically applied vancomycin. At the outset, 268 children aged 9–11 years were randomly assigned to the experimental or control group. Subjects in the experimental group were treated with a 3 per cent vancomycin gel applied in pretrimmed plastic trays for 5 min on school days. Plaque samples were taken every 4–6 weeks over a 12-month period from one sound occlusal surface, two sound approximal surfaces and one sound smooth surface. The surfaces assayed were the same at each sampling. Strep. mutans populations were determined in these samples using a selective medium. Significant reductions in numbers were observed consistently in occlusal surfaces. Sporadic and less pronounced effects were detectable on approximal and smooth surfaces. The treatment effects disappeared when treatment was suspended during the summer and re-appeared when treatment was resumed after the vacation.