A method of in situ hybridization with entire chromosome-specific DNA libraries for visualizing individual human chromosomes has been developed and applied to the detection of structural aberrations in both metaphase and interphase cells. Unlabeled human genomic DNA is used to inhibit the cross-hybridization of repetitive sequences in the library that bind to multiple chromosomes. The remaining single-stranded DNA is hybridized to specimens of interest and detected with fluorescent or enzyme labeled biotin conjugates following post-hybridization washes. This general approach is called "chromosome painting" or "chromosomal in situ suppression (CISS)" hybridization. In the present report, DNA inserts from recombinant libraries from chromosomes 1, 4, and 9 has been applied on controls and patients in order to decorate specifically their complementary chromosomes. Numerical changes, deletions and chromosomal translocations involving these chromosomes can be strikingly visualized.