Hi,
This is my first posting, and to some it may seem like a ridiculous question. I just got a
45-70 cowboy, my first big rifle, as I've always been a handgun person. When I first
shot it, I was shooting 405 gr. bullets with 5744 powder, and consistently hitting 1" groups
at 50 yards. I bought and reloaded some 4198, as I had run out of 5744 and now can hit
nothing. My question is: can changing powder really make that much difference, or should
I look elsewhere for the culprit? Thanks!

Yes it can make that much difference and often does.