Christopher Smith, who allegedly sent a billion, was arrested at a Minneapolis airport after he stepped off a plane from the Dominican Republic.
Smith allegedly had been operating illegal online pharmacies and a call center in the Dominican Republic, according to a representative for the Justice Department.
In May, a federal judge froze Smith's assets and issued a temporary restraining order barring Smith from selling prescription drugs. The online pharmacies allegedly let people buy prescription drugs without authorization from a licensed physician.
Last week, a judge issued an arrest warrant for Smith for allegedly violating the restraining order.
The case is currently a civil matter, but a criminal investigation is also under way, the representative said.
Although Smith's arrest and restraining order did not specifically address the spam issue, security experts rank Smith among their most prolific offenders.
"He was well up in our top 10," Steve Linford, chief executive of Spamhaus, said in an interview with News.com's sister site Silicon.com. Spamhaus is a nonprofit group based in the United Kingdom that tracks movements of alleged spammers.
That sentiment is shared by security experts from Sophos.
"Rizler has been one of the most notorious spammers, and anyone who has been deluged with spam offering medication and drugs will welcome the U.S. authorities making progress in the case," Graham Cluley, senior technology consultant at Sophos, said in a statement.
Will Sturgeon of Silicon.com contributed to this report from London.