The cytidine analogue 5-azadeoxycytidine (5-azadC) induces a very distinct inhibition of condensation in the genetically inactive, late-replicating X chromosome (XL) when applied to human lymphocyte cultures. One of the two X chromosomes in cytogenetically normal female cells becomes dramatically longer than its homologous partner. The highest rate of metaphases with an undercondensed XL chromosome is achieved when 5-aza-dC is added at a final concentration of 10(-5) M 2 h before cell harvesting. The interactions between 5-aza-dC and chromosomal DNA as well as the factors involved in X chromosome inactivation are discussed.