To test the hypothesis that meiotic nondisjunction may be caused by reduced chiasma frequency, hence recombination, we investigated 60 families with a trisomic child affected with Down syndrome (DS). We analyzed cytogenetic heteromorphisms (CH) and a number of restriction fragment length polymorphisms spanning regions 11.1 through 22.3 of 21q in both parents, in the DS child and, when available (21 families), in a normal sib. The parental origin and meiotic stage of nondisjunction were determined by combining the results of both CH and RFLP analysis. Crossover events were detected as switches in the parental haplotype expected in both DS and normal sibs. Available recombination frequency data were used to calculate the expected number of crossover events in nondisjoined and in normally segregating chromosomes, given the allele combination present in each family. The observed number of crossover events in normal meioses and in second-division nondisjunctions were consistent with the calculated figures. However, a significant reduction in the observed number of crossover events was found in nondisjoined chromosomes derived from errors in the first meiotic division and, in particular, in the proximal portion of 21q.