Early development in Xenopus laevis is controlled by maternal gene products synthesized during oogen-esis. The dorsal/ventral and anterior/posterior axes are established as a result of canonical Wnt signaling activity. The functions of maternal genes in embryonic development are most effectively studied by introducing anti-sense, oligos complementary to their mRNAs into oocytes and culturing the oocytes long enough to allow for the breakdown of the target RNAs and the turnover of existing cognate proteins before fertilization. This method has been used to establish the role of Wnt signaling in Xenopus axis formation. Here we describe the methodology for targeting of maternal mRNAs and for successful fertilization of mRNA-depleted oocytes.