We investigated an unusually large and severe outbreak of hepatitis B, primarily involving parenteral drug abusers and their sexual contacts, in Worcester, Massachusetts, over a 21-month period from 1983 to 1985. Of 135 patients with drug-related acute hepatitis B, 81 percent were parenteral drug abusers and 19 percent had sexual contact with drug abusers; 13 fulminant cases resulted in 11 deaths. Among the patients with hepatitis B, evidence of delta virus infection was found in 54 percent of drug abusers, 33 percent of their sexual contacts, and 9 percent of other patients with acute hepatitis B (P less than 0.001). Most of the delta infections (86 percent) were coinfections with hepatitis B virus; the balance were superinfections. Delta infection was strongly associated with fulminant hepatitis: 91 percent of patients with a fulminant outcome had delta infection, as compared with 45 percent of less severely ill drug abusers and their contacts (P = 0.0037). Alcohol, other drugs, and other hepatitis viruses could not be implicated as hepatotoxic cofactors for fulminant disease. This outbreak appeared to result from the concurrent spread of hepatitis B and delta viruses among new drug users. Control measures included the distribution to physicians of guidelines on prophylaxis in contacts of patients with hepatitis B, health education for drug abusers, and a hepatitis B vaccination program. Despite these efforts, the outbreak continued unabated until the number of new cases began to decline slowly in late 1986.