Between 1961 and 1978 seven outbreaks of Oropouche (ORO) virus have been documented in Pará State, Brazil. The clinical picture of ORO infection is characterized by fever, chills, headache, muscle pain, arthralgia, and other minor clinical manifestations. No deaths have to date been attributed to the disease but a proportion of patients become severely ill, occasionally to the point of prostration. Recurrence of symptoms has been observed in some patients, especially within the first 10 days after the initial symptoms. In some patients asthenia was noted for a period of 2–4 weeks. Outbreaks of ORO virus occurred in both small and large urban centers. In the largest urban centers the virus was limited to certain districts, whereas in villages the agent was spread throughout. Dissemination of ORO virus to several localities was observed in the 1967 Bragança and in the 1975 Santarém outbreaks. Over 30,000 persons became infected during these epidemics. All age groups were affected and the female:male attack rate varied from 1:1 to 3:1 in the different localities. Culicoides paraensis and Culex quinquefasciatus were the most common anthropophilic hematophagous arthropods in the epidemic areas. Virological and epidemiological evidence points to C. paraensis as the main urban vector of ORO virus. Successful experimental transmissions by the bite of C. paraensis further support the role of this midge as a vector. About 10% of patients infected with ORO virus develop viremia levels capable of infecting C. paraensis. It is conceivable that the urban cycle of ORO virus involves a man-to-man cycle maintained by C. paraensis. Since the maximum duration of the urban cycle is apparently only 6 months it seems likely that the virus is perpetuated by a sylvatic cycle. It is possible that certain species of primates, sloths, and wild birds can act as vertebrate hosts for the virus. Little is known, however, about the forest vector of ORO virus.