Pregnant sheep used in perinatel research were the source of a large outbreak of Q fever in 1980 among the faculty and staff of a medical school. Complement-fixation tests with phase II Coxiella burnetii antigen were positive in 81 persons, of whom 58 (71.6%) had Q fever during the first eight months of 1980. Microagglutination and/or indirect immunofluorescence tests of 485 sera were positive in an additional 56 persons. Only 41 of the 137 seropositive persons were involved in caring for or working with sheep; the remaining 96(70.1%) persons were located along the routes followed by sheep carts or had been exposed to sheep in other ways. Early in the outbreak few patients sought medical help. Later, most patients reported promptly and responded favorably to therapy with tetracycline. Sheep were removed from the campus in July 1980; cases ceased one month later. Other medical centers engaged in research with pregnant sheep should be alert to the risk of Q fever.