Magnetic resonance imaging with high static magnetic fields (SMFs) has become widely used for medical imaging purposes because SMFs cause fewer genotoxic side effects than ionizing radiation (IR). However, the effect of exposure to high SMFs on global transcription is little understood. We demonstrate that genes involved in motor activity, actin binding, cell adhesion, and cuticles are transiently and specifically induced following exposure to 3 or 5 T SMF in the experimental model metazoan Caenorhabditis elegans. In addition, transient induction of hsp12 family genes was observed after SMF exposure. The small-heat shock protein gene hsp16 was also induced but to a much lesser extent, and the LacZ-stained population of hsp-16.1::lacZ transgenic worms did not significantly increase after exposure to SMFs with or without a second stressor, mild heat shock. Several genes encoding apoptotic cell-death activators and secreted surface proteins were upregulated after IR, but were not induced by SMFs. Real-time quantitative RT-PCR analyses for 12 of these genes confirmed these expression differences between worms exposed to SMFs and IR. In contrast to IR, exposure to high SMFs did not induce DNA double-strand breaks or germline cell apoptosis during meiosis. These results suggest that the response of C. elegans to high SMFs is unique and capable of adjustment during long exposure, and that this treatment may be less hazardous than other therapeutic tools.