This study explored the mechanisms of toxicity of microcystins by measuring the transcription levels of nine cytoskeletal genes (actin, tubulin, vimentin, ezrin, radixin, moesin, MAP1b, tau, stathmin) in the liver, kidney and spleen of male Wistar rats treated with microcystins at a dose of 80 μg MC-LReq kg −1 bw. Microcystins disrupted the transcriptional homeostasis of cytoskeletal genes in these organs. Changes in the transcription of four genes (β-actin, ezrin, radixin and tau) in liver, one gene (stathmin) in kidney, and one gene (radixin) in spleen were significantly correlated with the tissue concentration of microcystins. However, the influences on the transcription of most genes we studied were greater in the liver than in the kidney or spleen. The effects of microcystins on the transcription of cytoskeletal genes may explain some of the morphological and pathological changes observed in these organs and provide new information on the hepatotoxicity of these compounds. Additionally, transcriptional changes in tumor-associated cytoskeletal genes (ezrin, moesin and stathmin) that were observed in the present study provide a possible clue to the tumor-promoting potential of microcystins and their influences on the transcription of MAP1b and tau imply possible neurological toxicity of microcystins in vertebrates.