Armed police swooped on a coach on the M6 Toll motorway in the West Midlands.
A police source told BBC Radio WM a passenger was seen pouring a liquid into a box, which then started smoking.
The 48 passengers on the Megabus Preston to London service were led off the coach and forced to sit apart in a cordon on the opposite carriageway.
A police spokesperson said: "We received a report from a genuinely concerned member of the public about suspicious activity on a coach travelling on the M6 toll at Weeford, near Lichfield.
"Given the nature of the report we responded swiftly and proportionately, treating the information as credible and extremely seriously.
"The M6 Toll carriageways were closed in both directions, the coach was directed to the hard shoulder of the motorway and armed officers calmly evacuated passengers with their full support and co-operation.
Armed police officers could be seen next to the single-decker coach on the southbound carriageway, as passengers were led off one by one.
Passengers were made to sit on the northbound carriageway, apart from one another, while surrounded by officers.
Sniffer dogs and forensic officers were also brought in to aid the search, as officers in forensic suits and others in military fatigues checked the area.
The Ministry of Defence confirmed military personnel were assisting police, at their request, under routine procedure.
One of the passengers on the bus told the BBC that she had no idea what was going on, that she didn't see anything supsicious, and wasn't told why they were pulled over.
She was made to sit cross-legged on the tarmac and still was not told what was happening. She said the whole experience had been very "scary and frightening".
Air con warning
The fire service, police from the West Midlands and Staffordshire forces and ambulance crews were all involved in the operation.
Nick Jones, a sales manager from Cambridge, said he was about four vehicles behind the coach when police stopped traffic.
"I've never seen so many ambulances turning up, also armed police, helicopter and dozens of police cars.
"We were told to stay in our cars, keep windows up and not put air conditioning on.
"Police were looking in hedgerows and verges on the northbound carriageway.
"It all just took off, ambulances left right and centre and armed police in black caps."
Another eye-witness Barry Jarvis told the BBC that cars were cleared from toll booths.
He said: "It was very puzzling as to what was going on at first as there weren't that many police there.
"It was only after 20 minutes or so when all these unmarked cars [were] coming through that we thought something major was happening.
"As we were diverted, we could see armed police at the toll booths, and the fire brigade."
Motorists on the M6 itself were experiencing delays of up to two-and-a-half hours.
And after all that:
Police said reports of vapour escaping from a bag which led to the security alert was caused by "a health improvement aid for smokers".
The motorway was closed between junctions T3 and T4 near Lichfield before police said they were no longer treating the incident as suspicious, but it has now reopened.
"Following an initial assessment, we can confirm that no-one has been injured and that there is no danger to passengers at the scene or any other travellers who were on the motorway at that time.
"We are also not treating anyone as a suspect."
