Although interferon (IFN) alpha and beta are currently recognized as the most effective agents for treating patients with chronic hepatitis B and C, they are well known to cause various adverse effects. To reduce the dose of IFN necessary for treatment, we tried enhancing the effects of IFN in the liver by ultrasound exposure. Percutaneous insonation in mouse liver following IFN-beta injection with the ultrasound power level used at clinical diagnosis enhanced the IFN-beta-induced increase of 2',5'-oligoadenylate synthetase (2-5AS) levels in the liver. This enhancement of the 2-5AS level was dependent on the duration as well as on the timing of insonation after the IFN-beta injection. In contrast, liver insonation did not enhance 2-5AS levels in the lung or spleen, and moreover, it did not alter tissue distribution of injected IFN. Thus, the combination of IFN-beta administration and subsequent liver insonation appears to be a promising method for enhancing the antiviral activity of IFN specifically in the liver, enabling a reduction in the dose necessary for treatment.