Police in Pennsylvania urged people not to look for or capture the cynomolgus macaque monkey after the crash on Friday afternoon on a state highway in Montour county.
"Anyone who sees or locates the monkey is asked not to approach, attempt to catch, or come in contact with the monkey. Please call 911 immediately," troopers tweeted.
Several monkeys escaped after the crash between the pick-up and a rubbish truck but as of Saturday morning only one remained unaccounted for, officials said.
The Pennsylvania Game Commission and other agencies searched for it amid freezing weather.
The US Centers for Disease Control and Prevention said the agency was providing "technical assistance" to state police.
The shipment of monkeys was en route to a CDC-approved quarantine facility after arriving on Friday morning at New York's Kennedy Airport from Mauritius, the agency said.
The truck had been on its way to a lab, Trooper Andrea Pelachick told The Daily Item newspaper of Sunbury.
The location of the lab and the type of research for which the monkeys were destined were not clear but cynomolgus monkeys are often used in medical studies.
A 2015 paper posted on the website of the National Center for Biotechnology Information referred to them as the most widely used primate in preclinical toxicology studies.
Trooper Laura Lesher said state police secured the scene for the Pennsylvania Department of Health and the US Centers for Disease Control and Prevention.
The condition and whereabouts of the remaining monkeys were not clear on Saturday.
The condition of the motorists also was not clear, nor was it clear whether any citations were issued.
Crash witness Michelle Fallon told the Press Enterprise newspaper of Bloomsburg that she spoke with the pick-up driver and a passenger after the crash.
The driver appeared to be disoriented and the passenger thought he might have injured his legs, she said.
Crates littered the road on Friday as police searched for monkeys, rifles in hand.
Firefighters used thermal imaging to try to locate the animals and a helicopter also assisted, the Press Enterprise newspaper reported.
The pick-up was heading west on I-80 when it got off at the Danville exit and then immediately tried to get back on, driving across the other lane, the newspaper reported.
Fallon told the Press Enterprise that she was behind the pick-up when it was hit on the passenger side by the rubbish truck, tearing off the front panel of the trailer and sending more than a dozen crates tumbling out.
She and another motorist who stopped to help were standing near the scene when the other driver said he thought he saw a cat run across the road, Fallon said.
Fallon peeked into a crate and saw a small monkey looking back at her, she told the newspaper.
"They're monkeys," she told the other motorist.