Epstein-Barr virus nuclear antigen leader protein (EBNA-LP) is important for primary B-lymphocyte growth transformation. We now demonstrate that the W repeat-encoded domain of EBNA-LP significantly associates with proteins of the heat shock protein 70 family (hsp72/hsc73). hsp72/hsc73 may mediate the previously observed interaction between EBNA-LP and the retinoblastoma protein or p53.