PIP: Trisomy, occurring in at least 4% of pregnancies, is the most common chromosome abnormality in humans. The majority of trisomies are associated with single additional chromosome. The presence of an additional sex chromosome is often associated with physical, behavioral, and intellectual impairment. The presence of an additional autosome is even more serious, being associated with severe mental and physical retardation and frequently with death in infancy. This review discusses the incidence, parental origin, and etiology of human trisomy. The incidence of trisomy varies widely among different chromosomes. This variation appears to reflect a real difference in the frequency of the primary event leading to trisomy as well as in differential selection. Studies of parental origin have shown a 1st maternal meiotic division error to be the most frequent source of the additional chromosome, regardless of the chromosome involved or the maternal age. Although the magnitude of risk varies among chromosomes, increased maternal age is an important risk factor in trisomy. The incidence of trisomy 21 increases from .05% of livebirths at maternal age 20 years to over 3% of all livebirths at age 45 years. The effect of maternal age is most pronounced in double trisomies. It has been hypothesized that the relationship between increasing maternal age and trisomy is due to a gradient in the fetal ovary that affects chiasma freequency. While the basis for the maternal age effect remains unknown, it is almost certainly due to factors acting at or before conception. Epidemiologic studies suggest that maternal irradiation exposure may also lead to trisomy; however, the effective dosage level and the relationship to maternal age remain unknown. No effect of oral contraceptives, spermicides, or fertility drugs on the incidence of trisomy has been documented to date. Understanding of the mechanisms by which trisomies are produced represents a major challenge for human cytogenetics.