Two members of a tour group were taken to a hospital in Colorado Springs after complaints of being sick.
The group was with a Diamond Tour group from Washington state, and most of them are senior citizens.
They were staying at the Comfort Inn on Harrison Road near Interstate 25 and Lake Drive.
It took the group about 18 hours to get to Colorado, and more than half of them are sick with intestinal problems.
Emergency medical teams said they think it may be a viral or bacterial disease that spread on the bus.
Firefighters initially thought the guests may have suffered from carbon monoxide poisoning, but ruled that out after checking all of the guest rooms at the hotel.
Emergency crews also considered food poisoning to be a possibility, but ruled that out.
Firefighters said they notified the Centers for Disease Control because the tour group was from out of state.
Medical technicians will be conducting blood tests to determine the exact cause of the illness.