Abrupt increases of alanine transaminase were observed in 6 of 23 non-treated, male homosexuals with chronic hepatitis associated with hepatitis B virus. Before this occurrence, all subjects had hepatitis B e antigen (HBeAg) and elevated DNA polymerase activity. Within 3 months, HBeAg was nondetectable in 3 subjects and elevated DNA polymerase disappeared in 4. These serologic events were not always sustained, however. In 3 subjects, reactivation of hepatitis B virus infection occurred within the subsequent 6-month period. Serologic testing for cytomegalovirus, Epstein-Barr virus, delta agent, and hepatitis B surface antigen (HBsAg) subtype showed that episodes of clearance and reactivation were not explainable by secondary infection with these agents or infection with a different HBsAg subtype. Spontaneous clearance and reactivation of hepatitis B virus infection may commonly occur among male homosexuals with chronic type B hepatitis. These phenomena should be considered when evaluating the need for treatment or interpreting the results of investigations that use anti-viral therapy.