On the basis of previous observations in chromosomes 21 and 22, we hypothesize that there is a tissue-specific organization of cardiovascular gene transcripts in the human genome. To examine the distribution of heart-derived transcripts, we assigned a nonredundant set of 4628 fetal and 3574 adult known and uncharacterized cardiovascular expressed-sequence tags (cvESTs) to 5-Mb chromosomal 'windows' on the basis of publicly available sequence mapping data. On a whole-genome level (36,617 genes), chromosome 17 (19.2% in fetal, 16.5% in adult) contained the highest proportion of cvESTs, whereas chromosome Y (2.0% in fetal and adult) contained the lowest. In total, 50 of the 639 windows contained a significantly higher proportion of cvESTs (P < 0.003) compared with the genome-wide cvEST gene density, particularly on gene-dense chromosomes (that is, 17, 19, 22) as opposed to gene-rich chromosomes (for example, 1, 2, 11). This report provides insight into a possible role for complex tissue-specific gene regulation in the human genome.