In any field, the prediction of future technology is a risky venture. One need only skim through a pile of popular scientific magazines from 20 years ago to resurrect a long list of beautiful, but unimplemented, technologies, ranging from helium-filled sky cranes to weeds that exude high-grade motor oil. In the face of uncertainty, technology prediction relies on three basic ideas. New technologies are (1) driven by demand, (2) in competition with the economics of established methods, and (3) limited by the available materials and systems for designing and fabricating tools.In basic science, few areas have witnessed technical changes of the magnitude observed recently in DNA and RNA analysis. To continue this advance, future analytical devices must balance cost and accuracy with the rapidly increasing demand for genetic information. The long-term potential of any proposed nucleic acid analysis system will be linked to the efficiency of its construction methods. Photolithographic rnicrofabrication is a mature technology developed and optimized by the computer microprocessor industry. The modern silicon-based microprocessor is an example of a monolithic integrated system, with each device containing large numbers of compatible components formed on a single substrate. Uniform replicate devices are produced economically in large batches using photographic templates. In a similar manner, photolithographic microfabrication may provide a candidate technology to build integrated nucleic acid analysis systems having improved sample throughput, accuracy, and cost efficiency.This paper presents a perspective of nucleic acid analysis, its compatibility with silicon microfabrication strategies, and future prospects for merging the two. Microfabricated devices for biochemical and fluidic manipulation are undergoing rapid development in many laboratories around the world (RamSCorresponding author. E-MAIL dtburke@umich.edu; FAX (313) 763-3784. sey et al. 1995; McIntyre 1996). Although an attempt to cover the range of published research efforts has been made, this is not a comprehensive review.