Abstract: One way to construct an exotic R^4 is to remove a slice disk from the 4-ball, replace it with a Casson handle, and then delete the boundary. In the 90's De Michelis and Freedman asked how the choices in this construction affect the smooth type. Since then, this problem has seen some progress but is still not well understood. Our main result is that if two slice knots have sufficiently different knot Floer homology, then the resulting exotic R^4's made with the simplest Casson handle are distinct. This allows us to distinguish an explicit infinite family of exotic R^4's. Our main tool is Gadgil's end Floer homology, which we compute effectively by analyzing Heegaard Floer cobordism maps. We also discuss new phenomena related to these R^4's, and relevance to the open problem of finding infinitely many smooth structures on all noncompact 4 manifolds. This is joint work with Jen Hom, Tye Lidman, and Shunyu Wan.