OBJECTIVES: Follicular non-Hodgkin's lymphoma (FL) is the most common indolent lymphoma occurring in the Western Hemisphere with a variable clinical course. Because of high costs of new treatments, we assessed direct health care costs associated with the most commonly prescribed treatments for FL. METHODS: New and previously diagnosed FL patients (>18 years) known during 1997 - 1998 to 15 Dutch hospitals were randomly selected for inclusion. Each patient was followed for three years, from a distinct event in the disease course onwards, for resource use associated with each of the treatments, including ‘watchful waiting'. The hospital perspective was adopted. Unit costs were based on the 2003 price level. RESULTS: Two hundred patients were included, of whom 75% percent underwent > 1 treatment during the 3-year data collection period (25% was not treated because of a watchful waiting strategy (10%) or complete remission (15%)). Allogeneic and autologous stem cell transplantations were the most expensive treatments, with a mean per patient cost of €45,326 (n = 7) and €18,866 (n = 9) respectively (up to discharge only). This was followed by fludarabine i.v. €10,651 (n = 33), rituximab (€10,628; n = 7), and CHOP €7547 (n = 42). Classical FL treatments were found to be the least expensive treatments used with an estimated cost for CVP of €5268 (n = 58), for radiotherapy of €4218 (n = 52), and for chlorambucil of €2476 (n = 53). CONCLUSIONS: This study presents detailed information on resource use and costs associated with the most commonly prescribed FL treatments. In addition to differences in effectiveness, commonly used treatments vary considerably in terms of resource use and overall cost. This information is of value for resource planning.