Differences in radio-sensitivity and tumour susceptibility in various strains of mice are well recognised. Among several commonly used inbred mouse strains, BALB/c has been consistently found to be sensitive to the development of various types of radiation-induced tumours. To elucidate the role of host genetic factors in radiation responses and to identify candidate susceptibility genes, we compared expression profiles in the liver tissue of C57BL/6 and BALB/c mouse strains following low-dose ionising radiation (LDR) exposure using microarray experiments. The two mouse strains showed significant differences in their gene expression profiles in response to radiation exposure. The differences were mainly in MAP-kinase and ubiquitin mediated signal transduction pathways. Thirty seven genes were identified which showed contrasting expression pattern between the two strains. Thus, we propose that different genetic backgrounds of the two strains play an important role in the differential activation of the cascades of signal transduction processes in response to LDR.