A large mumps outbreak occurred among students at a Kansas university in 2006. To reduce transmission, students with mumps were asked to isolate themselves. We describe isolation measures and student compliance with these measures. Questionnaires were administered to students suspected of having mumps. Of the 132 students instructed to stay isolated, 75% stayed isolated for the number of days recommended and were considered compliant. Case-students told to stay isolated for 1–4 days were more likely to be compliant [86% vs. 66%; adjusted odds ratio (aOR) 3·6, 95% CI 1·4–9·0] than those told to stay isolated for 5–9 days. Those who rated avoiding contact with others during isolation as very important were also more likely to be compliant (83% vs. 60%; aOR 3·6, 95% CI 1·5–8·4) than those who rated the importance lower. In a college setting, it may be difficult to achieve high compliance with guidelines recommending that persons stay isolated for much longer than 4 days.