A unique 2.2-kb mRNA is transcribed from the Q6 and Q8 genes of the mouse major histocompatibility complex. RNase protection experiments and DNA sequence analysis have mapped the 3 j terminus to a site located 1110 bp downstream from exon 8. Comparison of the 3' sequence of Q8 to that of Q7 revealed that the two genes diverge from one another at a point located 200 bp into the untranslated domain. This finding explains the increased size of the transcript. RNase protection experiments involving twelve different strains of mice have revealed few sequence polymorphisms. A tissue distribution of the 2.2-kb transcript in B6 mice revealed that the highest quantities of message were present in the spleen with decreasingly lower amounts in the thymus, liver, kidney, testis, and brain. The H-2" haptotype appeared novel; it is phenotypically Qa-2-, yet expressed a 2.2-kb transcript which hybridizes to a Q8 probe. A comparison of a Qa-2 hi expressor, B6, and a Qa-2 l°w expressor, BALB/cFla, has established that these quantitative cell surface differences are reflected in mRNA differences. A homology search of the Genbank database has revealed that the 3' portion of Q8 contains extensive homology to a retrovirus-like long terminal repeat sequence that is characteristic of an embryonic-specific transposon (ETn).