Jason,
From the NI-Serial manual (page 7-17 in the version I found
here) it seems that the red light on a port indicates that the port is open but there are no signals (ie nothing connected to the port). The port being open would certainly impair your ability to open it in another application since only one application can have it open at a time. So, in order to "unlock" your port, you need to close it in the original application that opened it.
I experimented with my USB-232 device and it seems that it's looking any one of a number of pins (like DSR, DTR, RxD, TxD) to be connected to a mark or space voltage before it changes the port LED to green, just in case you were wondering what the difference wa
s. In any case, if the LED is lit at all, then the port is open.
Scott