To define more exactly the epidemiology of delta virus infection and confirm its role in causing fulminant Labrea hepatitis in the Amazon Basin, we studied the prevalence of delta virus infection among persons with acute and chronic hepatitis B virus infection in the Boca do Acre district of the southern Amazon Basin. Delta virus infection was found in 24% of asymptomatic hepatitis B virus carriers, 29% of acute nonfulminant hepatitis B cases, 74% of fulminant hepatitis B cases, and 100% of chronic hepatitis B cases. Chronic delta virus infection occurred primarily in older children and adults, while acute and fulminant delta virus infection occurred in young children as well. In fulminant hepatitis cases, delta virus superinfection of hepatitis B virus carriers was the most common serological pattern; histopathologic examination showed features identical to those described in fulminant hepatitis cases of similar etiology in Colombia and Venezuela. Delta virus infection is highly endemic in the southern Amazon Basin and is the principal cause of Labrea hepatitis.