In human and primate studies, the presence of circulating antibody and C4d staining is associated with a variety of clinical phenotypes ranging from minimal to fulminant. But even when the clinical findings are minimal the time dependency of some of these phenotypes should invite caution before predicting the risk of future problems in an organ with C4d and circulating donor-specific antibody. See also articles by Haas et al on page 1829, Colvin et al on page 1790, Gloor et al in this issue on page 1841, and the minireview by Soleimani et al in this issue on page 1781.