During a 5-year period, an enzyme-linked antiglobulin test was used to screen and quantitate fetal-maternal hemorrhage in 789 consecutive D-negative mothers who were delivered of D-positive babies. Six hundred seventy-two patients (85.2%) had no detectable fetal-maternal hemorrhage, and 117 patients (14.8%) had a detectable fetal-maternal hemorrhage. Eight of the 789 (1%) had a fetal-maternal hemorrhage greater than 30 ml and required more than one vial of Rh immune globulin. Two patients with fetal-maternal hemorrhage of 29 and 30 ml also received additional Rh immune globulin. Each case was reviewed for the presence of high-risk features that are thought to predict patients at risk for fetal-maternal hemorrhage. Patients having a cesarean section or complicated vaginal delivery were considered to be in a group at high risk for fetal-maternal hemorrhage, while those with a spontaneous vaginal delivery were considered not to be at risk for fetal-maternal hemorrhage. Thirty-two of 237 patients (13.5%) in the risk group and 82 of 552 patients (15.3%) in the group not at risk had detectable fetal-maternal hemorrhage. The incidence of fetal-maternal hemorrhage for these two groups was not statistically different (p greater than 0.50 by chi 2 analysis). If only patients in the risk group had been screened for fetal-maternal hemorrhage, then five of 10 (50%) who required more than one vial of Rh immune globulin would have been undertreated and at risk for developing anti-D antibodies. In addition, newborn birth weight, Apgar scores, and hematocrits were examined for 13 cases of fetal-maternal hemorrhage of greater than or equal to 21 ml, and none of these characteristics could be used to predict patients at risk for fetal-maternal hemorrhage. Therefore, no maternal or newborn characteristics could be identified that would reliably predict patients at risk for fetal-maternal hemorrhage. We conclude that all D-negative patients with D-positive babies should continue to be screened for fetal-maternal hemorrhage to identify those patients requiring more than one vial of Rh immune globulin.