Yes it could matter. I assume you have XP, so my advice is to convert your C drive to ntfs.
To do this open a command prompt and type
"convert c: /fs:ntfs" without the quotes.
You will get a message that the conversion cannot take place because the drive is in use. Set it convert at the next reboot, and restart your computer.
ntfs will provide more stability, and permit larger file sizes.
If your OS is 98 or ME do not convert.