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I've found PyGTK is a joy to use, but the major downside for me is that it doesn't use native controls.

It mimics them with a theme on Windows, so presumably it looks okay (though I suspect it misses the finer details).

But on OSX, with its very distinctive widgets, GTK just looks horrible :(

Qt's a bit better than GTK on OS X, but it's still, sadly, not great. Qt tend to look out of place on OS X. Some of it seems curable -- e.g. simple things like getting margins right and so on, and other things are more complicated since in places Qt is trying to support interface elements that aren't used on OS X.

You can kind of see this with a few high-profile Qt apps like Google Earth, Opera, and the Last.fm client, the last being the best looking, but mostly because Max has put a lot of effort into making it not look like ass.

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