OBJECTIVES: The objective of this study was to estimate the direct annual cost of treating patients with schizophrenia in Greece, in 2005. METHODS: Due to the lack of quantitative data, information on the treatment pathway and medical resource utilization of patients were collected from a consensus panel of 9 psychiatrists representing different medical settings and geographic regions and 5 health economists. For estimating costs a bottom up approach from the National Health System perspective was used. Cost analysis included personnel salaries, diagnostic procedures, medication, outpatient visits, hospitalization and stay in supervised dwelling. Due to the variations between hospital pricing and reimbursement, three-scenarios were used to account for variability on hospitalization costs. RESULTS: The panel of experts defined three patient categories based on the severity of the disease and the medical setting where treatment is received: (a) outpatient setting (50% probability of hospitalization for 20 days per year); (b) ambulatory care (100% probability of hospitalization for 50 days per year); and (c) inpatient setting (100% probability of hospitalization for 60 days per year and 40% probability of 305-day stay in protected dwelling). The annual direct cost of treatment per patient was found to be: €3187 (€2659-€4,166) in the first category, €10,135 (€7,429-€13,972) in the second category and €20,782 (€17,482-€25,462) in the third category. The total cost of treatment increased with the severity of the disease and the use of hospitalization, while the contribution of medication to the total cost decreased compared to other cost attributes. CONCLUSIONS: The provision of health care to schizophrenic patients has a high cost for the health care system. Systematic data collection on medical resource utilization must be established at the national level to facilitate further research and guide the efficient use of resources.