Since the precise interactions of the various newt limb blastema cell types (pleiomorphic, bipolar, signet and multinucleated cells) with one another are difficult to ascertain in vivo, in this study we describe the in vitro behavior and interactions of these cell types with one another. The data show that the mononuclear signet cells interact (fuse) with other signet cells or fuse directly with the multinucleated cells. Further, they indicate that the signet cells are in fact mononuclear leukocytes and the giant cells are osteoclasts. Therefore, we conclude that these two cell types are not formed by dedifferentiation but are of hematopoietic origin and may play minor roles in blastema production.