We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon beta (IFN-beta) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-beta in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-beta genes mixed with microbubbles. Successful sonotransfection with IFN-beta gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-beta gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers. (C) 2011 Elsevier Inc. All rights reserved.