We describe the epidemiological and clinical features of human Murray Valley encephalitis (MVE) and Kunjin (KUN) virus infections in Western Australia (WA) during March to July 2000. A case series was performed. For laboratory-confirmed cases, travel histories and clinical details were collected from patients, family members, friends or treating physicians. Surveillance data from the sentinel chicken program and climatic conditions were reviewed. Nine encephalitic cases of MVE were recorded. Eight were non-Aboriginal adults (age range, 25 to 79 years; 5 male, 3 female) and 1 was an Aboriginal boy. Four cases acquired infection in the Murchison and Midwest regions of WA from which no human cases of MVE have been reported previously. One of the 9 cases was fatal and 3 had severe neurological sequelae. Five non-encephalitic infections were also recorded, 3 MVE and 2 KUN. Encephalitis caused by MVE virus remains a serious problem with no improvement in clinical outcomes in the last 25 years. Excessive rainfall with widespread flooding in the northern two-thirds of WA provided ideal conditions for mosquito breeding and favoured southerly spread of the virus into new and more heavily populated areas. Surveillance in WA with sentinel chickens and mosquito trapping needs expansion to define the boundaries of MVE virus activity. To enable timely warnings to the public, and to institute mosquito control where feasible, continued surveillance in all Australian areas at risk is indicated.