ABC said it learned from sources in the United States and Spain that the Armstrong investigation relates to doping activities spelled out in a U.S. Anti Doping Agency report.
Armstrong was a resident of Girona, Spain, for several years during his seven-year reign as Tour de France champion.
Under Spanish law it isn't a crime for an athlete to use performance-enhancing drugs, however, "trafficking, distribution and commercialization of doping drugs" is a criminal offense that carries a prison term and fine in Spain.
Spanish sources said authorities will decide if charges should be brought against Armstrong and his Spanish associates.
ABC said its sources described the investigation as being in a "very active and sensitive" phase.
An attorney for Armstrong didn't immediately respond to requests for comment.
Handler slams Piers Morgan: 'You're a terrible interviewer'
Astronomers offer more expansive view of universe