OBJECTIVES: To describe an outbreak and to identify risk factors for mumps occurring in a highly vaccinated high school population. (Note: Highly vaccinated means a population in which more than 95% have been vaccinated.) DESIGN AND PARTICIPANTS: Survey and cohort study of 307 (97%) of 318 students. OUTCOME MEASURES: mumps was defined as an illness with 2 or more days of parotid swelling. Serologic confirmation of infection was obtained in eight cases, seven of which were evaluated for presence of IgM antibody using immunofluorescent antibodies. Vaccination records were verified for 297 (97%) students. RESULTS: Between October 3 and November 23, 1990, clinical mumps developed in 54 students (attack rate, 18%), 53 of whom had been vaccinated. Most cases (40 [77%] of 52) occurred 12 to 20 days after a school-wide pep rally. Immunofluorescent antibody testing of all seven specimens demonstrated IgM antibody to mumps. Risk factors for clinical mumps identified in multivariate analyses included female gender (odds ratio, 3.0; 95% confidence interval, 1.6 to 5.7) and source of vaccination other than the local public health clinic (students vaccinated by private providers [odds ratio, 3.0; 95% confidence interval, 1.3 to 5.2] or in other districts [odds ratio, 2.4; 95% confidence interval, 1.1 to 5.3]). CONCLUSIONS: The overall attack rate is the highest reported to date (and to our knowledge) for a population demonstrating virtually complete mumps vaccine coverage. Even verified documentation of vaccination may not be an accurate indicator of an individual's protection against mumps. Vaccination failure may play an important role in contemporary mumps outbreaks. We found no evidence to indicate that waning immunity (secondary vaccine failure) contributed significantly to this outbreak. A second dose of mumps vaccine, as recommended using measles-mumps-rubella vaccine, could potentially prevent similar outbreaks in secondary school populations in the future.