In previous work, a reasonably large number of genes was found to be on chromosome 21. This frequency demands the creation of new techniques to investigate the transcription of this small human autosome, and to relate these findings to the phenotype of Down syndrome. Here we describe the elaboration of new vectors and hosts, which in conjunction with flow-sorted cosmid libraries of chromosome 21 and genic (cDNA) libraries of relevant human tissues, will permit us to examine transcription of chromosome 21.