Data from transcriptional mapping of human chromosome 21 have been compiled from a number of sources. Regardless of the gene identification technique used, a consistent picture has developed: the centromere proximal half of 21q, which contains 50% of the DNA (20 Mb), harbors only 10% of the expressed sequences. Because of the variety of gene isolation techniques used, this result is unlikely to arise simply from methodological artefacts, biases in clonability or tissue specificity of expression. This region is known to be AT-rich and to contain APP, the largest gene (spanning 300 kb) currently analyzed on 21q. Interesting preliminary data from analysis of the Fugu rubripes homolog of APP has shown an unusually high, 50-fold, compaction of intron size, raising the intriguing possibility that >90% of the DNA in the human gene may be functionless. Thus, data from a variety of approaches suggest that a large part of 21q very likely has neither coding capacity nor associated regulatory function. By these criteria, it is a good candidate for a repository of junk DNA.