Epidemiological data suggest a more favorable outcome of breast carcinoma in women taking cardiac glycosides. This study investigated whether digoxin could inhibit tumor growth in mice. Tumor growth experiments were done in mice grafted with the neuroblastoma cell lines SH-SY5Y, Neuro-2a, colonic cancer cells (LS174T) or Lewis lung cancer cells (LLC). Angiogenesis inhibition was investigated in vitro on fibroblast growth factor-2 (FGF-2)-stimulated bovine endothelial cell (BCE) growth and in vivo in the chick chorioallantoic membrane (CAM) assay. SH-SY5Y and Neuro-2a grafts were inhibited by 44% (p=0.008) and 19% (p=0.007), respectively, whereas the colonic cancer xenografts and LLC syngrafts were less responsive. The neuroblastoma specificity was confirmed in vitro. Digoxin also inhibited angiogenesis in the CAM assay and the BCE cell survival in vitro was 50% at 53 ng/ml. Our data suggest that digoxin may be a specific neuroblastoma growth inhibitor and an unspecific inhibitor of angiogenesis.