During a 2-year period, 38 patients with clinical hepatitis B virus infection were seen at the Public Health Service Alaska Native Hospital in Bethel. This hospital serves an area in southwest Alaska that is hyperendemic for hepatitis B virus. The patients came to the hospital at various times from 15 scattered villages, and 92% were Eskimo. None of the patients had a recent history of hypodermic injection or blood transfusions. Twenty-five patients, all originally positive for hepatitis B surface antigen (HBsAg), were followed for up to 5 years after onset of illness, and 15 were either slow to develop, or never developed, antibody to HBsAg (anti-HBs), although only one patient became a chronic carrier of HBsAg. Six patients had a prolonged "window phase" between the disappearance of HBsAg and the appearance of anti-HBs which lasted for more than 1 year. Three patients had only transient anti-HBs after HBsAg disappeared, and five never developed measurable anti-HBs at all. All patients had antibody to hepatitis B core when both HBsAg and anti-HBs were absent. In contrast to studies in other populations, only 42% had anti-HBs 1 year after onset of illness, 63% had it at 18 months, 70% had it at 2 years, and 80% had it at 5 years. Factors related to ethnicity might account for the differences in the development of anti-HBs after acute symptomatic hepatitis B virus infection seen in Eskimos when compared with whites.