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It happened around 8 a.m. Monday morning in rural Marseilles, about 75 miles southwest of downtown Chicago.
First responders quickly rescued and stabilized 60 children who were on board the school bus.
"Some were already out of the bus, and some were being removed through the escape hatches," said LaSalle County Sheriff Tom Templeton.
"It's a very difficult morning," said Milton Pope School District Superintendent Dave Hermann. "No one ever wants to see or hear of this type of accident with schoolchildren involved and school buses...we fortunately had the response people...on the scene immediately."
The LaSalle County Sheriff said the driver of a silver Dodge Dakota had a stop sign at the intersection of East 25th and North 32nd roads in Milton Township. The bus driver did not.
"It appears that the silver truck did get into the intersection and was hit right squarely in the center by the school bus as it came through the intersection," Templeton said.
Thirty-seven children were transported to area hospitals, as were to two drivers.
Despite the serious impact, none of the injuries appear life threatening.
"We're very fortunate the injuries are only what they were," said Templeton. "There were some serious injuries. People are being treated at local hospitals, but it could have been much, much worse."
The children, ranging in age from kindergarten through eighth grade, were just a couple of miles from Milton Pope School.
The district superintendent cancelled classes Monday as a quarter of the student body was involved in the accident.
The driver of the silver pickup was given a traffic citation. Forty-four-year-old Michael Shelton was cited for failure to yield at a stopped intersection.
Milton Pope School administrators plan to have counselors on duty Tuesday.