We examined Sprague-Dawley rat liver tissue and primary hepatocyte cells to understand how they compared in gene expression responses to hexahydro-1,3,5-trinitro-1,3,5- triazine (RDX). Gene expression was analyzed in primary cell cultures exposed to 7.5, 15, or 30 mg/L RDX for 24 and 48 hours. Cells were compared to liver from rats 24 hours after exposure to 12, 24, or 48 mg/Kg RDX. Similarity of present/absent calls to liver in control exposures was 88% at 24 hrs and 79% at 48 hrs. Significant changes were identified using mixed-model analysis of variance. Up to 6.4% of differentially expressed genes present in liver were differentially expressed in 24hr cells and less than 5.5% in 48 hr cells. Of genes with identifiable KEGG pathways, 24 hr cells 78.4% similar to liver pathways and 48hr cells were 44.3% similar. These data suggest care should be taken extrapolating effects from in vitro to in vivo levels.