Abstract: XP group C protein (XPC) and a human homologue of RAD23, HHR23B, have previously been shown to copurify in a tightly associated complex. Here, we show that XPC interacts in vivo, by means of the yeast two-hybrid system, with both HHR23B and a second homologue of RAD23, HHR23A. Domain mapping studies have revealed that both RAD23 homologues interact with XPC at the same highly conserved region in the C-terminal half of the protein. XPC mutants deleted within this domain and that are highly deficient in binding both RAD23 homologues are also highly defective in complementing XPC cells in vivo. Domain mapping studies have also identified a region in the N-terminal half of HHR23B that contains the XPC interactive site. This domain is highly conserved among HHR23B, HHR23A, and RAD23.