A friend of mine, from MD, is interested in getting into the shooting sports with a rifle, probably a regular 10/22.  I've bought rifles out of state in CO before, but how will it work of a Maryland resident?

Just have a local (MD) FFL receive the firearm for your friend. He should be able to find one near him.
Clayton Otto (Otto's Police Supply) is a good one, and probably the cheapest around at $30.00 for a regular long gun transfer like a 10/22.

Just my $.02; 10/22's are so commonly found, and relatively inexpensive (WalMart/Dick's/Sports Authority) that it would have to be a really special deal, or a really special rifle, to make it worth the transfer of funds, rifle shipping expense and the receiving FFL's fee . . .

I should have been more clear--we're both in CO for college right now, and he'd be doing the transfer in person.  For me, they can just run the background check because it is identical to what I would get in my home state.  Would they do the same thing for him?

I don't think its a problem.  He has to buy from an FFL, no exceptions.  He will fill out the 4473 with his MD address, FFL runs the check, and he gets his 10/22.  I think that the law merely states that the laws of both states shall be complied with.  As far as I know, neither MD nor CO has any restrictions on 10/22's above and beyond the federal requirements, so he should be good to go.

Depends on the store.I know of one that simply won't sell anything to MD residents (Or CA,NY,NJ,MA)even though they legally can.

Well, we've figured out some things, but some are still unknown.   CO has a requirement that buyers be from contiguous states.  We can avoid this by driving to Cheyenne.  Unfortunately, no one we've contacted yet will do the transfer.  I see several mentions here of MD residents buying in PA or VA, but not in other states.  Is there perhaps a Maryland law that requires MD residents to only buy in contiguous states?

Quoted: Well, we've figured out some things, but some are still unknown.   CO has a requirement that buyers be from contiguous states.  We can avoid this by driving to Cheyenne.  Unfortunately, no one we've contacted yet will do the transfer.  I see several mentions here of MD residents buying in PA or VA, but not in other states.  Is there perhaps a Maryland law that requires MD residents to only buy in contiguous states?

There is this:

Maryland Code
Public Safety
Title 5. Firearms
§ 5-204. Purchasers of rifles or shotguns.

(a)  "Adjacent state" defined.- In this section, "adjacent state" means Delaware, Pennsylvania, Virginia, or West Virginia.  
 
(b)  Resident of this State in adjacent state.- If a resident of this State is eligible to purchase a rifle or shotgun under the laws of an adjacent state, the resident may purchase a rifle or shotgun from a federally licensed gun dealer in the adjacent state.  


I do know Marylanders who have purchased long guns from dealers in non-adjacent states (and filled out federal and their states' paperwork), though.