Organ shortage for transplantation has focused attention on educational interventions. Italy is a nonhomogenous country whose cultural and economic differences are reflected in the health-care system: dialysis is mainly public in the north versus private in the south; and transplantation rates display a wide range from 3.4 to 37.8 per million people in 2002. The aim of the present study was to analyze the opinions of population of high school students (last two years) in two large cities: northern (Torino) and southern (Napoli) Italy, as a knowledge base for a randomized controlled trial on the efficacy of educational interventions on renal replacement therapy and organ donation, targeted to high school students. This preliminary study included eight public high schools that completed a first and anonymous semistructured questionnaire. Five hundred and eighty nine questionnaires were retrieved in Torino and 539 in Napoli. In both cities most students answered that they would give a kidney to a brother, sister, or partner needing dialysis (Torino: yes 80.6%; no 2.2%, uncertain-blank 17.2%; Napoli: yes 86.1%, no 1.1%; uncertain-blank 12.8%). Only 36.3% of the students in Torino and 37.7% in Napoli answered that they would consent to organ donation, if they had to choose for a strict relative with brain death. Opposition was 28% in Torino and 23.7% in Napoli; 35.7% in Torino and 38.6% in Napoli were blank-uncertain. These data underline the need for detailed information on the opinions of the overall population as basis for tailored educational campaigns.