Constitutional chromosomal abnormalities are an important cause of miscarriage, infertility, congenital anomalies and mental retardation in humans. Most human constitutional chromosomal imbalance results from aneuploidy, a condition that appears to be much more frequent in humans than in any other species studied. Chromosomal rearrangements and segmental deletions and duplications also occur in humans, but much less often. Although treatment of human somatic cells with some environmental agents produces chromosomal damage, no measurable increase in the frequency of constitutional chromosomal abnormalities has been unequivocally demonstrated among the children of parents exposed to any agent. Recent work has provided insight into a variety of mechanisms by which chromosomal abnormalities can arise during gametogenesis and early embryogenesis. Mechanisms have also been recognized that can correct or partially compensate for chromosomal imbalance, sometimes permitting survival of conceptuses that would otherwise be lost early in gestation. This improved understanding can be used to refine future studies of the cytogenetic effects of environmental exposures.