I'm a ESET Reseller and have experienced this twice now. Both servers are Windows Server 2008 R2 64-bit. One with Exchange 2007 (SBS 2008 ) and the other with Exchange 2010. I have followed the exclusion list for Exchange Servers to the T. Lockups can happen immediately or over time. No pattern other than removing ESET 4 latest build fixes the lockup issue. ESET support had me install 4.2 Beta, but still the lockup.