Twelve red kites and four buzzards have been found dead within two square miles to the south east of Conon Bridge near Dingwall, Ross-shire.
At least six were poisoned. The total number of raptors to have died that way during the whole of last year was six, with only three in 2012.
The bird charity has described the latest deaths as one of the worst campaigns of persecution it has encountered.
Scottish Gamekeepers Association chairman Alex Hogg described it as "unprecedented and alarming".
Duncan Orr-Ewing, head of species and land management for RSPB Scotland, said it was a shocking indictment of the behaviour of some in rural Scotland.
He contrasted what has happened to the Black Isle red kites with the fortunes of the same number released at the same time in the Chilterns in southern England. The population there is now 10 times bigger.
He said: "We are offering a £5,000 reward for information that leads to a conviction. We urge anyone with information to contact Police Scotland so the perpetrators can be identified."
The red kite was hunted to extinction in Scotland over a century ago, but between 1989 and 1994 the species was reintroduced in four areas.