We performed a strain intercross between two apoE-deficient mouse strains with a large difference in lesion susceptibility and measured aortic root lesion area in 98 female F(2) progeny. Total RNA was prepared from bone marrow-derived macrophages, and RNA from the five mice with the smallest and largest lesions were used for microarray gene expression profiling. Remarkably, approximately 5% of the 12,288 expressed transcripts were differentially expressed in the atherosclerosis-susceptible and atherosclerosis-resistant bone marrow-derived macrophages (unadjusted p < 0.05), thus defining the transcriptome of macrophages associated with atherosclerosis susceptibility. Using more stringent criteria of twofold or greater change and p < 0.01, 116 and 70 transcripts were overexpressed in lesion-prone and lesion-resistant bone marrow-derived macrophages, respectively. Transcription factor binding site analysis identified two promoter elements that were found more often in the genes overexpressed in the large-lesion group, and one promoter element that was found more often in the small-lesion group. The combination of this expression profiling data with the genetic method of quantitative trait locus mapping should give powerful insights into the genes that affect atherosclerosis susceptibility in mice.