People were killed, but state police did not immediately know how many.
A tanker truck may have spilled fuel and a tractor-trailer jackknifed and landed on its side during the 10:20 a.m. crash on Interstate 95, state police said.
"It's a significant accident," said Lt. J. Paul Vance, a state police spokesman.
Transportation officials said the accident would take seven to eight hours to clean up, snarling traffic on part of the key interstate highway in the Northeast corridor.
Firefighters were spraying foam as a precaution in a fuel spill, and state environmental officials were headed to the site.