The use of in situ hybridization for the identification of specific nucleic acid sequences in tissue sections has the potential for broad application in pathology. Although this technique has been successfully applied to routine paraffin sections, there have been few studies of the application of in situ hybridization to plastic-embedded tissue sections. The authors adapted techniques developed for paraffin sections to take advantage of the potential for improved morphology and more precise localization inherent in the plastic sections. A commercially available biotinylated DNA probe specific for the cytomegalovirus to develop a practical method for detection of nucleic acid sequences in plastic-embedded tissues was used. Using plastic sections, cytomegalovirus DNA sequences could readily be identified with precise localization of the virus and superb histology.