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Try Sparrow. I've been running their trial version as well. It is really good and 10$ for full version.

Agreed. I paid the $10 and I have not looked back. I really like this app.

I heard/read about issues with very large cache directories (with thousands of tiny files).

I have an ssd so the speed isn't a concern for me, but as osx lacks trim support, I am concerned about huge caches.

Have you seen or noticed the cache being overly large?

I do have a weird 'lag' when I get to my e-mail in the morning after being away all night. My system does not sleep, but Sparrow is unresponsive for about 60 seconds. But just then everyday. After that I am fine until the next morning. I am not sure if that relates at all.

I have a lot of e-mail and 'labels' and I seem to do just fine.

TRIM support is coming in Lion (OS X 10.7) but I am sure you know that since you know 10.6 doesn't have it. I still felt compelled to type it though...

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