The effect of glycyrrhizin on melanoma cells was investigated. DNA fragmentation in cultured melanoma cells was promoted by the addition of glycyrrhizin in a dose dependent manner. Administration(i.m.) of glycyrrhizin to Mel/ret transgenic mice resulted in apoptosis induction, reduction of mitochondrial transmembrane potential in melanoma cells. Decreased B220+ B cells were recovered by the treatment of glycyrrhizin in splenocytes and mesenteric lymph node cells, while Thy-1+ T cells were not influenced. Results suggested that glycyrrhizin acted as an inducer of apoptosis of melanoma cells and an immuno-potentiator via recovered B lymphocyte population in Mel/ret transgenic mice.