The development of a vaccine is essential for the elimination and eventual eradication of malaria. However, despite many years of effort, a successful malaria vaccine has not yet been achieved. Many of the subunit vaccine candidates tested in clinical trials have provided limited efficacy; therefore, efforts to develop an effective vaccine against malaria need to continue. The development of a whole parasite blood-stage vaccine would maximise the number of blood-stage antigens presented to the immune system, including conserved parasite antigens. Chemical treatment has been used to develop attenuated whole organism vaccines against pathogens, such as viruses. A blood-stage vaccine approach using DNA- binding drugs to chemically attenuate Plasmodium parasites was first demonstrated using ring stage Plasmodium chabaudi parasites in mice. However, it was not clear whether this approach would apply to other parasites and as such have potential for translation to human malaria species. We have thus tested the use of these drugs as attenuating agents for another blood-stage Plasmodium spp., Plasmodium yoelii.