A method to isolate specific regions of the Drosophila polytene chromosome using an atomic force microscope (AFM) was explored. The AFM was used for the microdissection of the locus of interest with much greater precision than standard microdissection techniques. The amplification of DNA isolated in this fashion by the polymerase chain reaction (PCR) is discussed. A study of the effect of hydration level on gross chromosome structure was carried out. It was shown that chromosome swelling is dependent upon humidity or the buffered medium. The significance of this swelling with respect to studies of chromosome structure under physiological conditions is considered