Brian and Marjorie Peacock have been hounded by protesters since moving into a property whose previous owner was singled out by the Animal Liberation Front.
In the latest incident on Saturday morning, they awoke to discover the front of their detached home had been daubed in two foot-high letters spelling out "ALF."
Police officers who carried out house-to-house inquiries said neighbours reported seeing two men with their faces covered.
Mr and Mrs Peacock are now at the end of their tethers – particularly as Brian, 65, is battling cancer.
He said: "I was diagnosed with non-Hodgkin's lymphoma four weeks ago and I'm not supposed to have any stress, but this is a nightmare.
"We have nothing whatsoever to do with animal testing.
"I was a consultant for the NatWest bank and my wife was a secretary. We just want these people to leave us alone."
The couple say the house, in Wentworth Way, Sandal, Wakefield, was previously owned by a man whose company deals with laboratory waste.
It is believed the address was placed on a list held by the activists, who don't realise he no longer lives there.
The Peacocks claim the seller failed to tell them of any potential problems when they bought the property two-and-a-half years ago.
They say the first inkling they had was six months after moving in, when they found the front of the house covered in paint on New Year's Eve and hundreds of Animal Liberation Front leaflets strewn across their front garden.
Brian said: "When that happened the police told us Special Branch were getting involved and they would make sure the address was taken off these people's list, but now it has happened again. I don't for one minute condone what these people are doing, but they should at least get their facts right. We can't take any more of this."
Marjorie, 66, said: "I am shaking. The police are saying it's not us they are targeting but the house – but that doesn't help in any way."
One of the couple's daughters, Joanne Gibbs, 37, begged the activists to now lay off her parents.
The Animal Liberation Front's website says the hardline group is committed to "direct action against animal abuse in the form of rescuing animals and causing financial loss to animal exploiters, usually through the damage and destruction of property."
grant.woodward@ypn.co.uk