Undergraduate courses in human physiology and pathophysiology often include an essay as part of the continuous assessment, with the intention of giving students experience in independently researching and writing, as well as increasing their understanding of a particular topic. Unfortunately, many of these essay questions may actually foster plagiarism because they can be answered by providing a factual explanation, which is readily available in texts and on the Internet. We describe a strategy for pre-empting such plagiarism, called the ‘hypothetical condition’ essay, where the instructor invents a fictitious but entirely plausible physiological condition or concept which students must evaluate and discuss. Since no specific background material is available, the student has to research the relevant normal and abnormal physiology and then use their knowledge to logically speculate on the effects of the fictitious condition, so the opportunities for plagiarism are greatly reduced. The hypothetical condition essay was trialled with a second level undergraduate human pathophysiology class in 2007. No cases of plagiarism were detected in the bulk of the essay where students presented their logical arguments on the effects of the new condition. Nor did students appear to be disadvantaged, since there was no significant difference in either the mean, or the variance, of marks among years before and after the new assessment was used. The hypothetical condition essay also appeared to foster originality and critical thought, and we suggest the concept of this type of assessment could be applied in many fields.