Sheep scab, caused by the mite Psoroptes ovis, is a notifiable disease in Switzerland. Mandatory prophylactic treatments are carried out in spring for all sheep grazing on common alpine pastures. Despite these strict control measures the number of outbreaks has been increasing in recent years, raising questions on the spread of this epizootic disease. To improve the traditional microscopic diagnosis, we developed an ELISA for the specific determination of antibodies against psoroptic antigens with sensitivity and specificity of 93.7 and 96.5%, respectively. Using this test, a serum bank, representative of the sheep population in Switzerland (approximately 15% of registered sheep flocks, randomly chosen, collected between February and May 1998), was screened. The prevalence using 16,404 sera was 10.4, and 11.9% of the 2083 flocks were diagnosed as positive. Additionally, there was a significant increase found for mean seropositivity relative to the flock size (P<0.001, linear regression). Therefore, larger flocks had a higher risk of sheep scab, which may be caused by more frequent animal movement. Spatial analysis of the results revealed a region with significantly higher risk (relative risk = 3.5, P<0.001) of seropositivity, where no cases have officially been notified in the period between 1997 and 1999. The next goal is to establish an efficient control strategy based on serological monitoring of the total sheep population.