An unusually large number of cases of mosquito-borne encephalitis occurred in Iowa in 1975. Nineteen St. Louis (SLE) cases were confirmed from 11 scattered counties in the state between the 2nd week of August and the end of September 1975. The second highest number of LaCrosse (LAC) (California group, family Bunyaviridae) encephalitis reported in a single year also occurred in 1975. In addition, 5 human and 434 equine cases of western equine encephalomyelitis (WEE) were reported from the western region of Iowa. In 1976, a tenfold decrease in the number of WEE cases in horses was noted. In addition, there were only 3 SLE and 5 LAC cases; 1976 was a year of unprecedented drought conditions that markedly reduced mosquito populations throughout the state. Virus activity in mosquitoes is discussed in relation to serologically confirmed cases in humans and clinical cases in equines. Culex pipiens populations were considerably larger in June and July 1974 and 1975 than they were in 1973 or 1976. A strong relationship between large mosquito population levels and mosquito-borne encephalitis existed in Iowa. Three SLE virus isolates were obtained from 38 pools (741 Culex mosquitoes) collected in late 1975. In contrast, only one SLE virus isolate had been obtained during a 12-year period from 41,652 Culex mosquitoes processed for virus isolation.