OBJECTIVES: To estimate the cost-effectiveness of a national rotavirus (RV) vaccination program for the Netherlands, from a societal perspective. METHODS: Three RV-vaccine doses are administered to infants as part of the routine schedule of childhood immunizations. Based on clinical trials we assume a vaccine protection duration of 4 years and a vaccine effectiveness of 55% against mild RV-diarrhea, 65% against moderate RV-diarrhea (outpatient treatment), and 80% against severe RV-diarrhea (inpatient treatment). Resource consumption caused by RV-diarrhea is derived from recent national studies and the findings of expert panels and valued according to the Dutch costing guidelines. Direct medical (e.g., for vaccine administration or RV-tests) and non-medical costs (e.g., for transportation or extra diapers) are considered. Indirect costs include the productivity loss of paid (friction cost method) and unpaid work (substitution approach) caused by parents caring for their sick child. Costs are presented in 1998 EUR and both future costs and effects are discounted at 4%. A decision analysis model is employed to calculate the health outcomes and costs of the vaccination program. RESULTS: RV-vaccination would avoid 34,300 cases of gastroenteritis and 2,300 hospitalizations per year. The break-even dose price of the vaccine is EUR 4 or EUR 9, depending on the exclusion or inclusion of the productivity loss of unpaid work. However, at a dose price of the 1999 withdrawn RV-vaccine (EUR 30) the program would yield costs of EUR 15,000 (paid work only) or EUR 12,100 (paid and unpaid work) per avoided hospitalization. These results are sensitive to the incidence of RV-gastroenteritis, the vaccine effectiveness, the length of hospitalization, and the productivity loss caused by RV-gastroenteritis while variations in outpatient care and direct non-medical costs have limited influence. CONCLUSIONS: Depending on its price the RV-vaccine might be a promising candidate for the Dutch national immunization program.