The four victims were freight train crew members, said the Arkansas State Police.
The collision occurred shortly after 2:30 a.m. on tracks near U.S. 67 between Hoxie and Minturn, said Jonesboro Police and Fire in a statement. A portion of the town of Hoxie was evacuated shortly after the crash, according to the Arkansas State Police.
Hoxie is south of Walnut Ridge, about 23 miles northwest of Jonesboro and 120 miles northeast of Little Rock, AK.
After the crash, a fire broke out, according to Arkansasonline.com. Crews initially attacked the fire, and were told the car on fire contained an alcoholic beverage, which, along with diesel fuel from the train, was feeding the flames, said Kendell Snyder, spokesman for Arkansas Department of Emergency Management. The blaze was still reported as burning at daybreak, but was not believed to be a threat to the toxic cargo, said police.
Both trains were carrying toxic materials, although it appears that none was released. He had not been briefed on what toxic substances were being carried, said Snyder.
Union Pacific officials were at the crash scene and will head an investigation, said Bill Sadler, spokesman for the Arkansas State Police.
"It's railroad property," said Sadler. "The mission of State Police right now is just to assist local authorities in keeping the roads blocked."
Evacuating part of south Hoxie was "precautionary" because the two Union Pacific trains were carrying "toxic cargo" and one engine caught on fire, said state police. At one point, officials were going door-to-door notifying residents to evacuate.
About 100 people were sheltered at a community center and a church in Walnut Ridge for a brief while, then returned to their homes.
The cause of the crash is unknown.