My first DG rifle was a Ruger "African" in .375 Ruger that I purchased in 2005 or so. I owned it for about six months, finally concluding I hated it. As a lover of fine firearms, it simply reminded me of something made in shop class. Soon thereafter, I acquired a custom .375 built on a FN action. I accounted for my first buffalo with it along with a slew of plains game.
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Next was a Blaser S2, because like many here, I found doubles fascinating. The S2 was particularly interesting because like the R8, barrels and calibers are interchangeable. Mine has 500/416, .375, and 30-06 chamberings. The .375 set accounted for my second buffalo and both it and the '06 barrels took plains game (out to 225 yards or so).
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Around this time, I had Craig Libhart build me a magnificent .404. It shoots sub MOA and would be a fine DG rifle. It has never been to Africa. Why? I am coming to that.
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Not long thereafter, I handled an R8 at a friend's shop in Maryland and I was smitten. Set up as a .375 it had the heft of a 30-06 and the OA length of a .308. Fit was as perfect as the custom Libhart. The barrel collection grew to include a .404 and three different stocks. But it was in .375 configuration that it accounted for my next two buffalo and a host of plains game from Sunni to eland.
Configured in classic sporter stock and standard .375 barrel
There has also been a fine English .470 (recently sold) and I won't count the 9.3x74R's. But it is a .375, the R8 in particular, that gets the nod for an actual hunt in Africa. There is, in my experience at least, nothing yet made quite so versatile and practical for anything in Africa than Holland & Holland's perfect creation.