Rationale and design of a study on the cost-effectiveness of the Dutch influenza vaccination campaign are described. During two influenza epidemics, about 75,000 primary care patients recommended for influenza vaccination are included. Cases have fatal or non-fatal influenza, pneumonia, otitis media, acute respiratory disease (ARD), heart failure, myocardial infarction, depression or diabetes dysregulation. Per case four controls are sampled, frequency matched on age and high-risk co-morbidity (< 18 years, 18-64, greater than or equal to65 healthy, greater than or equal to65 with co-morbidity). Baseline and outcome data are retrieved from patient records. During the 1999-2000 influenza A epidemic 5891 (7.9%) high-risk children, 24,848 (33.2%) high-risk adults aged 18-64 years, 18,484 (24.7%) elderly with co-morbidity and 25,527 (34.1%) healthy elderly had been included. The mortality rate was 5.2 per 1000 and 2035 non-fatal outcome events were recorded (incidence rate 27.2/1000). (C) 2002 Elsevier Science Ltd. All rights reserved.