The epidemiology of infection with the hepatis-B-virus (HBV)-associated delta agent was assessed from the prevalence of antibody to delta in 1206 HBsAg-seropositive subjects from various parts of the world. Anti-delta was prevalent in unselected HBsAg-positive Italians, whether residents in Italy or elsewhere, and in drug addicts and polytransfused HBsag carriers throughout the world, suggesting that delta-associated infection is spread through contact in Italy and parenterally in other countries. Parenteral transmission of the delta agent was confirmed by a separate survey of the prevalence of anti-delta in 648 polytransfused patients with chronic blood disorders, which showed a higher prevalence of anti-delta in HBsAg-positive haemophiliacs than in the general HBsAg-positive population of Italy, Germany, and the U.S.A. In view of the failure to detect delta in the absence of markers of HBV, the prevalence of anti-delta among polytransfused HBsAg carriers suggests that the delta-associated agent is transmitted by superinfection or coinfection of HBsAg carriers, the HBsAg carrier state possibly providing a rescue function to the superinfecting agent.