Hungary says traces of toxic red sludge from an industrial plant have now reached the river Danube, about 70km away.
Concerns have been raised that the highly alkaline mud could poison the Danube, Europe's second longest river.
Countries downstream from Hungary, including Croatia, Serbia and Romania, are drawing up emergency plans.
It is seen as Europe's worst ecological disaster since Chernobyl in 1986, when there was an accident at a nuclear power plant in the Ukraine (formerly part of the Soviet Union).
Disaster official Tibor Dobson said all life in the Marcal river, which feeds the Danube, had been extinguished.
Dead fish have been spotted in both the Danube and its tributary, the Raba.
To save their eco-system, Mr Dobson said pH levels must be reduced to 8 from about 9 recently recorded at the confluence of the Raba with the Danube.
Four people died when a million cubic metres of sludge surged through six villages in western Hungary on Monday. A state of emergency was declared on Tuesday.
The mud also caused massive damage in nearby villages and towns, as well as a wide swath of farmland.
The BBC reports the red sludge is waste from the early stages of aluminium production.
It contains a mixture of metal oxides. Between 40% and 45% is iron oxide, which gives the mud its characteristic red colour.
The sludge is a strong alkali, meaning it will cause burns when it comes into contact with the skin, and can damage lungs and the digestive system if it is ingested. This may cause death.