BACKGROUND: To evaluate the prognostic value of screening for irregular antibodies late in pregnancy (third trimester) in rhesus positive women. Only those cases where irregular antibodies have not previously been demonstrated during routine screening in the first trimester with regard to clinically relevant complications in the newborn, were studied. MATERIALS AND METHODS: All women living in Frederiksborg county and giving birth in 1996 (n = 4216) were assessed for inclusion in the study. This was done by gathering the files at the Hillerød and Hørsholm Hospitals' blood banks for antibody test results. Six hundred women were excluded because of the lack of either the rhesus type or the late antibody test. RESULTS: Of the 3616 women, 3046 were rhesus positive, and 3012 of these had a negative first trimester screen test. Fifteen of the 3012 women later developed irregular antibodies in the third trimester, and were included in the study. This corresponds to only 0.5%, and none of these cases entailed perinatal complications for the mother or the child. CONCLUSION: Routine screening of rhesus positive pregnant women in the third trimester is not rational from a cost-benefit perspective, if the only purpose is to prevent hemolytic disease of the newborn.