Some of the spatial cues which direct early patterning events in Drosophila embryogenesis are maternal mRNAs localized in the oocyte during oogenesis. For example, Bicaudal-D, fs (1) K10, and orb RNAs are transiently localized at the anterior oocyte margin in mid oogenesis, and oskar RNA is localized at the posterior oocyte margin beginning in mid oogenesis. Using inhibitors of cytoskeletal function, we find that microtubules, but not microfilaments, are required for localization of these mRNAs during oogenesis, results similar to those described earlier for bicoid RNA. However, the RNAs show a differential sensitivity to microtubule inhibitors. Anterior localization of Bicaudal-D, fs (1) K10, and orb RNAs is completely disrupted following even mild drug treatments. bicoid RNA localization is intermediate in its response to microtubule drugs, while oskar RNA localization is much more resistant. In addition, the localized RNAs respond differently to taxol, a microtubule stabilizing agent. The differences among these RNAs suggest that factors other than microtubules are required to maintain the positions of localized RNAs in the oocyte. Microtubules are also required for the preferential accumulation of these transcripts in the previtellogenic oocyte, consistent with the idea that these mRNAs are transported by a microtubule-dependent mechanism to the oocyte.