We have investigated the structure of the human HOX-2 locus, which encompasses a 90-kb region on chromosome 17q21. Five new human HOX-2 homeoboxes, termed HOX-2.5, 2.4, 2.6, 2.7 and 2.8, have been identified, and their nucleotide sequences are reported. They have the same 5'-3' transcriptional orientation and are clustered with three previously described HOX-2 homeoboxes (5'-2.5-2.4-2.3-2.2-2.1-2.6-2.7-2.8-3'). We have also investigated the region-specific expression of HOX-2 genes in human embryonic-fetal life by Northern-blot analysis. All genes are expressed in whole embryos and fetuses at 5-9 weeks from conception. Their major site of expression lies within the central nervous system (CNS), although they are transcribed at a lower level in body structures other than the CNS. Their relatively abundant expression in CNS has been analyzed along the anterior-posterior axis by dissecting the brain, the medulla oblongata and the spinal cord proper. HOX-2.5, 2.4 and 2.3 transcripts are markedly more abundant in spinal cord than in medulla, whereas 2.2, 2.1, 2.6 and 2.7 mRNAs are progressively more abundant in the medulla. Additionally, expression in brain was detected, although at lower level, for HOX-2.1, 2.6, 2.7, 2.8. Thus, the relative position of HOX-2 homeobox genes along the chromosome in the 5'-3' direction appears to correlate with the relative position of their expression domains along the CNS longitudinal axis in the caudal-cephalic direction.