In Drosophila melanogaster, deletions of the pericentromeric X heterochromatin cause X-Y nondisjunction, reduced male fertility and distorted sperm recovery ratios (meiotic drive) in combination with a normal Y chromosome and interact with Y-autosome translocations (T(Y;A)) to cause complete male sterility. The pericentromeric heterochromatin has been shown to contain the male-specific X-Y meiotic pairing sites, which consist mostly of a 240-bp repeated sequence in the intergenic spacers (IGS) of the rDNA repeats. The experiments in this paper address the relationship between X-Y pairing failure and the meiotic drive and sterility effects of Xh deletions. X-linked insertions either of complete rDNA repeats or of rDNA fragments that contain the IGS were found to suppress X-Y nondisjunction and meiotic drive in Xh-/Y males, and to restore fertility to Xh-/T(Y;A) males for eight of nine tested Y-autosome translocations. rDNA fragments devoid of IGS repeats proved incapable of suppressing either meiotic drive or chromosomal sterility. These results indicate that the various spermatogenic disruptions associated with X heterochromatic deletions are all consequences of X-Y pairing failure. We interpret these findings in terms of a novel model in which misalignment of chromosomes triggers a checkpoint that acts by disabling the spermatids that derive from affected spermatocytes.