We report the first use of a surface forces apparatus to study the hybridization of DNA. We study the regime of very high ionic strength (approximate to1 M) at which commercial DNA chip operations are performed. Using a thiol end-attached single-stranded oligonucleotide, we find that exposure to the complementary strand resulted in larger thickness. In addition, the resistance to small-amplitude shear deformations when opposed to a nonadsorbing surface (mica) increased significantly after hybridization. The thickness at onset of significant shear resistance was, for single-stranded DNA, considerably less than that of hybridized DNA. This could provide a new method to detect DNA hybridization efficiency.