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Tamiami virus, a member of the Tacaribe group of viruses, was first isolated in 1963 from cotton rats collected in the Tampa Bay area of Florida. In subsequent studies Tamiami virus appeared to circulate permanently in cotton-rat populations in the area. Suckling mice used for primary isolation do not always show clinical signs when infected material from cotton rats is injected intracerebrally. However, isolates made in this system indicate that about 10% of some population groups have virus present in tissue. Virus is isolated more frequently from young than from older animals, with no apparent seasonal variation in rates of isolation. Virus was recovered readily from urine, circulated for a short period in the blood of experimentally infected animals, and could have been shed in saliva. Transmission in nature probably occurs through contact with urine-contaminated food or bedding. and possibly by fighting. Although infected cotton rats may contaminate tomatoes and other field crops, persons apparently do not become infected by working in fields inhabitated by infected rats. No laboratory infection with this virus has yet been recognized. Its publichealth importance, therefore, still remains to be demonstrated.