Cycling's world ruling body says five cyclists will face doping charges uniquely on the basis of irregularities found in blood samples from their biological passports.
A former world road race champion Igor Astarloa of Spain is among the three Spaniards and two Italians who are facing doping charges.
The news comes just over a fortnight before the start of this year's Tour de France, although none of the riders snared by the UCI were expected to star at the three-week epic.
It will be the first time athletes who have not tested positive will face doping charges purely on the basis of their biological passports.
However it is not the first time a cyclist has been banned without failing a dope test. Italian star Ivan Basso was banned just over two years ago based on evidence linking him to the Operation Puerto affair.