I'm not... uncomfortable around them. But I can't say that conversation feels quite as natural around most of them. Probably because most women I encounter just have nothing in common with me, and it's hard to relate. It's sad, but the majority of girls at my university are kind of... boring.
Whenever I can find a member of the opposite sex whom I can relate to, social interaction is far easier.
Edit: When I like a girl, or, even worse, if she's into me, I have no idea how to act. People as chronically single as myself don't flirt very well. But I seem to be getting a bit of female attention lately, so I'm going to have to learn fast.