Mossel Bay police have seized perlemoen with a street value of R800 000.
The bust was made on the N2 on Thursday when police followed up on a tip-off.
They searched a bakkie and trailer and found 5 400 units of perlemoen hidden in metal containers covered with wooden planks.
Two men from Elsiesrivier and Bredasdorp were arrested and will appear in the Mossel Bay Magistrate's Court on Friday.
This is the seventh incident in five months where vehicles transporting perlemoen were pulled over on the N2 near Mossel Bay.