For some viruses, yes. Some will add extra files with obscure names in places you rarely look on your machine.

Others will "patch" your DLL's, making the size of DLL files grow. You could look on your Microsoft installation CD for the size of the DLL and make a comparison.

On the whole, given the number of viruses and the myriad of mechanisms, trying to detect anything but a specific virus by manual means is a losing proposition.