OBJECTIVES: A temporal relationship between the increasing use of antibiotics and the increasing levels of antibiotic resistance has been established for Streptococcus pneumoniae. There are also data that support the presence of a geographic correlation between the level of resistance and the pattern of use among different countries and even within the same country. The aim of this study was to evaluate the potential geographic correlation between the use of beta-lactams and erythromycin in different Italian regions and the resistance of these antibiotics to invasive strains of S. pneumoniae during the period 1999-2000. METHODS: Ecological study. RESULTS: In Italy the mean level of resistance for penicillin and erythromycin was 11.4% and 28.9%, respectively. The highest level of resistance for both antibiotics was observed in central and southern regions (i.e. Campania, Lazio and the combined regions of Calabria, Puglia and Sicilia). These regions were also those with the highest consumption of antibiotics. A strong correlation was found between the prevalence of resistance to erythromycin and the regional use of macrolides (r=0.93, P=0.001) and beta-lactams (r=0.84, P=0.002). With regard to penicillin resistance, the greatest correlation was observed for oral penicillin (r=0.85, P=0.002). CONCLUSION: Our study provides further evidence of the association between regional level of antibiotic use and prevalence of antibiotic resistance.