Uh... My brain hurts from just thinking about this...

You could make it a contextual ligature. Have a class consisting of all the glyphs in the font, and have it appear when nothing in the class proceeds the two glyphs in question.

Note that this could then get triggered by anything else that breaks the context, such as a change of font. Even a change within the same family (bold or italic, for instance) would do it....

T

Sounds to me like what you want is not contextual at all, since the space is part of the ligature. Surely you just make a space_thing1_thing2 ligature?

Thanks. I'll try Thomas suggestion. It sounds like a lot of CPU activity just for a ligature though.
No it is contextual of some sort. This ligature is ment to replace a specific word not the same characters within another word. This word wouldn't be a word inside the text without a preceding space. But it still would be a word at the begining of the line.
b

Sorry. I didn't read the second half of your post properly.