Altered recombination patterns along non-disjoined (NDJ) chromosomes (chrs.) is the first molecular correlate identified for non-disjunction in humans. In an earlier study we found strong evidence that specific recombination patterns along NDJ chrs. 21 are associated with an increased risk for most maternal meiotic errors. We have now extended our earlier study to determine the extent to which recombination may be altered in eggs with a NDJ chr. by asking if the altered recombination is a cell-wide phenomenon or if the effect is limited to the NDJ chr. 21. We attempted to enrich our study population for extreme deviations from normal variation in recombination by examining only Down syndrome cases due to maternal meiosis I errors that had no detectable chr. 21 recombination events (n=17). Female meiotic events from the CEPH families were used as controls (n=91). Using 366 genome-wide markers, we assayed for cell-wide disturbances in the amount of recombination. The genotypes from the maternal grandparents, parents, and case or control offspring were used in a conventional linkage study to detect recombination along maternally-transmitted chrs., excluding chr.21 and Y. A statistically significant reduction in total recombination was observed between the cases and controls, 35.9 ± 6.7 vs. 39.9 ± 6.8, respectively (p < 0.02). This reduction did not seem to be due to any particular chr(s)., rather it was cell-wide; however, the power to detect such variation was low. Our results provide the first evidence for a cell-wide reduction in the amount of recombination occurring in human eggs with NDJ, non-crossover chrs. 21. This novel finding advances the understanding of recombination-associated non-disjunction in humans by suggesting that a trans-acting factor(s) related to the meiotic recombination process, rather than a chr. 21 cis-acting factor, may underlie a subset of human meiotic non-disjunction events.