To investigate the prevalence and clinical features of hepatitis D virus infection (HDV) in childhood, total antibody to hepatitis D antigen (anti-HD) in serum samples from 247 children (29 with acute hepatitis B, 68 with chronic hepatitis B, and 150 with asymptomatic hepatitis B surface antigen (HBsAg) carriers with normal liver function profiles) were studied using solid-phase competitive radioimmunoassay. Anti-HD was detected in three of the 29 children with acute hepatitis B and in only one of the 68 with chronic hepatitis B; none of the serum specimens from 150 asymptomatic carriers with normal liver function profile showed detectable anti-HD. All three children with HDV coinfection cleared HBsAg and seroconverted to anti-HBs, whereas one with superinfection finally had normal liver function without clearance of HBsAg. To identify possible sources of HDV infection, HBV markers and anti-HD in family members were also examined. One 4-month-old infant boy became infected through a blood transfusion from his hepatitis B e antigen (HBeAg)-positive carrier father, who had anti-HD. A 4-month-old infant girl was infected through close contact with her HBeAg-negative carrier father, who had HDV superinfection. The infection sources remained undefined in another two patients. The mothers of these four children were seronegative for anti-HD, indicating that perinatal transmission is not the usual mode of HDV infection in Taiwan. The natural course of either acute or chronic HBV infections in childhood in Taiwan may be more closely related to HBV itself, or to some other yet unrecognized factor, rather than to HDV infection.