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Context Basic science teaching in undergraduate medical education faces several challenges. One prominent discussion is focused on the relevance of biomedical knowledge to the development and integration of clinical knowledge. Although the value of basic science knowledge is generally emphasised, theoretical positions on the relative role of this knowledge and the optimal approach to its instruction differ. The present paper addresses whether and to what extent biomedical knowledge is related to the development of clinical knowledge. Methods We analysed repeated-measures data for performances on basic science and clinical knowledge assessments. A sample of 598 medical students on a traditional curriculum participated in the study. The entire study covered a developmental phase of 2 years of medical education. Structural equation modelling was used to analyse the temporal relationship between biomedical knowledge and the acquisition of clinical knowledge. Results At the point at which formal basic science education ends and clinical training begins, students show the highest levels of biomedical knowledge. The present data suggest a decline in basic science knowledge that is complemented by a growth in clinical knowledge. Statistical comparison of several structural equation models revealed that the model to best explain the data specified unidirectional relationships between earlier states of biomedical knowledge and subsequent changes in clinical knowledge. However, the parameter estimates indicate that this association is negative. Discussion Our analysis suggests a negative relationship between earlier levels of basic science knowledge and subsequent gains in clinical knowledge. We discuss the limitations of the present study, such as the educational context in which it was conducted and its non-experimental nature. Although the present results do not necessarily contradict the relevance of basic sciences, we speculate on mechanisms that might be related to our findings. We conclude that our results hint at possibly critical issues in basic science education that have been rarely addressed thus far. [ABSTRACT FROM AUTHOR]