Molecular analysis of structural chromosomal abnormalities, involving the sex chromosomes, has provided us new knowledge concerning sex determination in humans. This has raised three hypotheses of sexual differentiation, which will be discussed even though none of these can explain all abnormalities involved. Meiotic recombination which normally takes place during the male meiotic cell division, can give rise to sex reversal syndromes such as XX male and XY female, if crossing over is abnormal. Analysis of these abnormalities has made it possible to map sex determining regions on chromosome Y, and to construct a deletion map. Methods using DNA probes, are capable of identifying Y-specific sequences in persons with sex reversal. This means a more optimal counselling, possibilities of prenatal diagnosis, and opportunities for selecting patients with risk of gonad cancers, for extirpation.