OBJECTIVES: To determine the demands on health care resources caused by disease, age and gender and to demonstrate the importance of the perspective on health expenditure (national versus international). METHODS: A generic top-down cost-of-illness analysis was performed for the Netherlands. Expenditure per provider in 2003 was known for three perspectives on healthcare costs: the OECD's System of Health Accounts (SHA) and two national perspectives. Data on health care use were collected from 70 registries of which the most important had national coverage. These were mapped on expenditure to estimate cost of illness and enabled analysis in six dimensions: provider, health care function, source of funding, age, gender and disease. Outcome measures were total costs and costs per capita. RESULTS: Mental diseases represent the most expensive main diagnostic group (22% of total costs). Heart diseases come second (9.2%). Neoplasms come on a 7th place (4.1%). The three perspectives showed minor differences in ranking of disease groups. Total costs differed widely between perspectives: €43.7 to €57.5 billion (9-12% GDP), the higher estimate based on the perspective of the Dutch National Health Accounts, the lower on the perspective of the Dutch ministry of Health. The international SHA-perspective came close in total costs to the ministry of Health estimate (€45.1 billion), but had a radical different composition. Cost increase by age, sharply from 65+ onwards until €50.000 per citizen for the oldest old. In the SHA-approach the increase is less steep because of the exclusion of specific health provisions for Dutch elderly. CONCLUSION: The perspective on health expenditure has an important influence on coi-estimates, especially for per capita costs and to a lesser extent for the relative expenditure on particular diseases. Insight in the differences between perspectives enables better national and international comparisons between coi-studies.