To assess the epidemiology of infection with the delta agent associated with hepatitis B virus, sera from 1314 carriers of the hepatitis B surface antigen (HBsAg) and 687 patients with hepatitis B collected in 1978-1981 from different regions of Italy were tested for delta antigen and antibody to the antigen (anti-delta), and the characteristics of delta-positive patients were analyzed. Anti-delta was found in each center participating in the study, indicating that delta infection has spread throughout Italy. Its prevalence was higher in carriers in southern Italy and in those with chronic hepatitis. In northern Italy, delta infection predominated among southern emigrants in industrial towns but also among parenteral drug addicts with hepatitis B virus infection. The prevalence of delta markers was variable and generally low in acute hepatitis B, suggesting that in Italy self-limited forms of delta infection occur sporadically or by limited outbreaks. Delta infection appears to be endemic in southern Italy but a new epidemiologic event in northern Italy, where it was probably introduced by southern emigrants and is presently exceeding its ethnic confinement to spread selectively in communities of drug addicts. Presumably, the endemicity of delta is maintained by transmission of this agent from carrier to carrier of the HBsAg.