I have been fascinated by chromosomes for longer than I care to mention; their beautiful structure, cell-type-specific changes in morphology, and elegant movements delight me. Shortly before I began graduate study, the development of nucleic acid hybridization made it possible to compare two nucleic acids whether or not their sequences were known. From this stemmed a progression of development in tools and techniques that continues to enhance our understanding of how chromosomes function. As my PhD project I contributed to this progression by developing in situ hybridization, a technique for hybridization to nucleic acids within their cellular context. Early studies with this technique initiated several lines of research, two of which I describe here, that I have pursued to this day. First, analysis of RNA populations by hybridization to polytene chromosomes (a proto-microarray-type experiment) led us to characterize levels of regulation during heat shock beyond those recognizable by puffing studies. We found also that one still-undeciphered major heat shock puff encodes a novel set of RNAs for which we propose a regulatory role. Second, localization of various multicopy DNA sequences has suggested roles for them in chromosome structure: Most recently we have found that Drosophila telomeres consist of and are maintained by special non-LTR (long terminal repeat) retrotransposons.