Caterpillar nuclei (CN) are characterized by their peculiar morphology, with chromatin distributed in clusters and running along the longitudinal axis of the nucleus. They can be observed in normal hearts of fetuses as well as in hearts of children and adults with rheumatic heart disease. This study has demonstrated by means of ploidy studies with digital image analysis that in the fetal heart (20.5+/-1.8 weeks) the CN (diploid = 5.6+/-8.4%; tetraploid = 46.2+/-24.2%; hypertetraploid = 46.9+/-26.3%) present higher DNA content than non-caterpillar myocyte nuclei (diploid = 89.4+/-6.2%; tetraploid = 10.0+/-4.1%; hypertetraploid = 1.5+/-1.3%) (P=0.000001, 0.00013, and 0.000038, respectively). Expression of proliferation cell nuclear antigen (PCNA; 30.6+/-11.7% in CN and 13.4+/-7.3% in non-caterpillar myocyte nuclei; P=0.0115) and cyclin B1 (2.8+/-3.8% and 12.6+/-15.6%, respectively; P=n.s.) was also positive in these nuclei. In conclusion, these results suggest that there exists a relationship between CN morphology and myocyte replication phenomena.