In a pilot study aimed to test the therapeutic potential of beta interferon (IFN) given intramuscularly we treated 4 patients with HBeAg positive chronic hepatitis B with a progressively increased dosage of beta IFN (from 5 to 9 million units daily) for 1 month and with 9 million units for 5 additional months, thrice weekly. In 3 of the 4 patients, serum HBV-DNA decreased during therapy and remained undetectable in 2 who seroconverted from HBeAg to anti-HBe while in 1 patient viraemia rebounded to pretreatment levels during the follow-up. In the remaining patient serum HBV-DNA fluctuated during treatment. These results suggest that beta IFN given intramuscularly has a potential therapeutic efficacy in patients with chronic hepatitis B and prompt further clinical trials in a larger number of patients.