I'm about to upgrade my company's old Exchange Server hardware, which is wearing out. I'd like to buy AMD Opteron-based servers and run one of the Windows Server 2003 x64 Editions to give us room for future growth. But will Exchange Server 2003 run on this configuration? What do you recommend?
No. Microsoft doesn't support Exchange 2003 on Windows 2003 x64 Editions and is unlikely to do so in the future. The current release of Exchange 2003 won't even run on the Windows 32–on–Windows-64 (WOW64) subsystem, which allows many other 32-bit applications to run on 64-bit systems.
I know you're probably disappointed to learn this news, but a sound technical reason exists. Exchange 2003 and Exchange 2000 Server depend on the Exchange Installable File System (ExIFS) driver, a 32-bit piece of code that runs in kernel mode. For Windows 2003 x64 Editions, all kernel-mode code must be native 64-bit. ExIFS isn't, and Microsoft isn't planning to spend the necessary resources to make it so.
The larger question is what Microsoft will do with the next release of Exchange (code-named Exchange 12). As of this writing, the company hasn't announced any firm plans for x64 support in Exchange 12. However, Dell, HP, and IBM are all briskly selling servers with 64-bit–capable hardware, so it's safe to assume that Exchange 12 will feature some kind of 64-bit support. I recommend replacing your hardware now with servers that can support 64-bit Windows but holding off on the upgrade to Windows 2003 x64. Instead, install the 32-bit version and wait to upgrade until there's a version of Exchange (and ancillary products such as antivirus and backup software) that can take advantage of the x64 extensions.