The EpiAir Project evaluated the short term effects of air pollution on mortality and morbidity in 10 Italian cities (Milano, Mestre-Venezia, Torino, Bologna, Firenze, Pisa, Roma, Taranto, Cagliari e Palermo) during the period 2001-2005. A time-stratified case-crossover design was adopted, with results equivalent to those found using the traditional time series approach. The levels of PM10, NO2 and ozone measured in the Italian cities during the study period were higher than the reference European standards and the World Health Organization guidelines indicating a persistent exposure of Italian people to toxic air pollutants. The results of the EpiAir study showed higher effect estimates for mortality related to PM10 and NO2 than those reported in international studies and in previous Italian analyses. The percentage increase of natural mortality associated with a 10 microg/m3 increase in PM10 concentration was 0.69%, while it was 0.33% in Europe (APHEA study), 0.29% in North America (NNMAPS study) and 0.31% in the previous Italian meta-analysis of data collected in the nineties (MISA study). An important effect of PM10 and NO2 has been observed on hospitalizations for acute cardiac diseases, in particular myocardial infarction and heart failure, while NO2 increased the frequency of hospital admissions for respiratory diseases, especially asthma. The lag time between exposure and health effects was immediate for cardiovascular diseases and delayed for respiratory diseases. The study considered several susceptibility factors and elderly subjects were found to be more vulnerable to PM10 effects. The findings suggest the need for continuous epidemiologic surveillance of the health effects of air pollutants in Italy together with immediate national and local preventive programmes.