Forty people are being investigated in connection with historical child sexual abuse and exploitation offences in Rotherham.
It relates to 13 people aged between 11 and 26 at the time of the alleged offences between 1997 and 2015.
The 38 men and two women were arrested or interviewed by appointment over the last two months, said the National Crime Agency (NCA).
All have been bailed or released under investigation as enquiries continue.
They are aged between 29 and 53 and from Sheffield, Rotherham, Leeds, Dewsbury and Maidstone.
The arrests are part of the ongoing Operation Stovewood investigation into the abuse and exploitation of more than 1,500 children in the South Yorkshire town.
Six trials have already been held under Stovewood since November 2017, with more than a dozen men jailed.
In the most recent trial, in October and November last year, seven men were convicted of abusing five girls aged under 16 and received sentences of up to 23 years.
They were found guilty of charges including rape and aiding and abetting rape.
Carl Vessey-Baitson, from the NCA, said Operation Stovewood showed the "desire to listen to victims and bring offenders to justice is not wavering".
He said it was the largest investigation into non-familial CSAE (child sexual abuse and exploitation) ever undertaken in the UK.
Other investigations into years of abuse of young girls in the town - Operation Clover and Operation Thunder - have seen more than 20 other men jailed in recent years.
Arshid Hussain from Goole has received the longest sentence, getting 35 years after a trial in February 2016.
The investigations began after a 2014 report by Professor Alexis Jay detailed the rape, grooming and trafficking of more than 1,400 children.
That figure has now been updated by the NCA to 1,523.