Two high school students died and at least 23 were injured when a school bus has plunged off the interstate highway and overturned 30 metres below.

The school bus was carrying 34 students of Lee High School in Huntsville, Alabama, it has been reported.

The bus was returning from the Huntsville Center for Technology where students can receive special science and math credits, city schools spokesman Keith Ward said.

"It looks like the bus plunged head first," police spokesman Wendell Johnson said, adding that police is "trying to stabilize injuries, save lives."

No information about injured students, seven of which suffered critical injuries, is not available at this point.

There was no immediate information on what may have caused the bus to jump off the highway. The driver's condition has not been released.