A sensitive, reproducible assay for detecting Renibacterium salmoninarum in a variety of tissues, including blood, has been developed. This assay, based on reverse transcription-polymerase chain reaction (RT-PCR) of 16S ribosomal RNA, exhibited sensitivity to </=10 cells per milligram of tissue by ethidium bromide detection, and this sensitivity was increased 10-fold by Southern blotting. There was a strong association (p <.001) between blood and ovarian fluid for the presence of bacteria in spawning salmon, and in 17.9% of the infected fish, bacteria were detected in blood but not in ovarian fluid. The ability to analyze multiple tissues, the reproducibility, and sensitivity of 16S RT-PCR make it a useful tool for both research and husbandry applications.