The Wnt pathway and the recently described Xenopus homeobox gene Siamois share the ability to mimic Nieuwkoop organizer signaling activity when ectopically expressed, prompting us to ask whether the Wnt pathway can activate Siamois expression. We show that activators of the Wnt pathway, and the dorsalizing substance LiCl, activate Siamois expression in Xenopus animal caps. Furthermore, Siamois expression is shown to be activated by beta-catenin cell-autonomously. Although certain TGF-beta family members, such as Vg1, are potent dorsal mesoderm inducers, the TGF-beta pathway only weakly activated Siamois. Finally, we demonstrate that Siamois expression is eliminated from the marginal zone of UV-irradiated Xenopus embryos, supporting the hypothesis that cortical rotation moves a Wnt-like activity into the dorsal region. These results suggest that formation of the Nieuwkoop organizer is dependent on activation of Siamois by a localized Wnt-like signaling activity, which may act synergistically with a vegetally localized TGF-beta signal.