Brothers Mako and Billy Vunipola have left England's tour of South Africa after Eddie Jones' side suffered defeat in the second Test.
Saracens forward Billy re-fractured his arm during the first half of the clash in Bloemfontein and will be assessed further during the week.
His brother, also at Saracens, is returning to England for family reasons which were agreed with team management before the tour.
Ellis Genge is also on the way home after he suffered a knee injury in training during the week.
Exeter Chiefs' Alec Hepburn has been called in as a replacement and will join the squad at their training base near Durban before the third and final Test against the Springboks in Cape Town next Saturday.
Hepburn, 25 has two previous England caps, both from this year's Six Nations -- the most recent picked up against Wales at Twickenham in February.
Saturday's Test defeat was England's fifth in a row and leaves them just one game away from an unwanted record.
Should South Africa win again in Cape Town they would not only secure a series whitewash but also inflict England's sixth Test defeat in a row to make it their worst losing streak since 2006.
The pressure is mounting on head coach Eddie Jones whose 17-match winning streak at the start of his tenure now seems a distant memory.
The Tasmanian described England's latest setback as 'a bit like a horror movie'.
"We made errors in different areas of the game today. We are trying to work out why we did that. our plan of how we wanted to play the game going into it was pretty clear, but as soon as something small happens we just don't seem to react to it on the field at the moment."
"This team has got a lot of pride, we have won back-to-back Six Nations, we have equalled the world record for number of Test wins in a row, we have gone to Australia and won 3-0."
"Now we are going through this bloody tough period. Everybody is going to work extremely hard to get out of this and it will be an absolute top effort in Cape Town."