purpose: To determine the incidence of adverse reactions to hepatitis B plasma-derived vaccine. patients: Alaska natives (43,618) who received 101,360 doses of hepatitis B vaccine. methods: All adverse reactions, excluding transient fever, myalgia, or soreness lasting less than 3 days, were reported. An intradermal skin test was developed to test purported adverse reactions. Records of the entire population were reviewed for Guillain-Barre syndrome (GBS). setting: A statewide hepatitis B control program for Alaska natives. results: Possible adverse reactions occurred in 39 persons. The most frequent adverse reactions were myalgia/arthralgia lasting longer than 3 days (14), followed by skin rashes (eight) and dizziness (seven). Skin tests were performed on 13 persons and were positive in five. Six of the persons with negative skin tests and eight persons who did not undergo skin testing received additional doses of vaccine without any adverse reactions. No increased incidence of GBS was found in the vaccinees. conclusion: Hepatitis B vaccine is safe and most adverse reactions are coincidental.