This one comes with a big red notice:

Important Instructions
Before installing and developing with the sixth beta versions of the iPhone OS and SDK, you must first upgrade your Mac system to Mac OS X v10.5.3. To upgrade your Mac, go to System Preferences and select Software Update to install the latest version.
App IDs are a new requirement in provisioning profiles for iPhone OS beta 6. To continue developing, Team Admins will need to create App IDs and regenerate all provisioning profiles. Previously generated provisioning profiles will not work with iPhone OS beta 6.

Sparse info from the What’s New section of the readme as usual:

Beta release 6 requires the Leopard 10.5.3 software update and is incompatible with other OS releases and pre-release software. This release fixes many bugs and add support for the latest iPhone OS.