Our three cases represent the spectrum of findings when maternal anti-M is present. In the first case, the father's genetic makeup (NN) indicated no disease would occur. In the second case, despite antibody capable of crossing the placenta, the infant did not become sick. In the third case, hemolytic anemia required transfusion of the newborn, despite a negative direct Coombs' (DAT). In summary, anti-M antibody is an uncommon cause of hemolytic disease of the newborn. When anti-M, IgG optimally reactive at 37 degrees C, is identified in the maternal blood, the paternal blood must be checked for the presence of M antigen. If the father has M antigen the fetus may be at risk. Since there is no documented body of experience that titers of anti-M predict severity of disease, our recommendation is that amniotic fluid bilirubin studies be done, in spite of the fact that only one prior case of hemolytic disease due to anti-M was found reported from the United States. Anti-M is an unpredictable antibody and serial antibody titers are not reliable. After delivery the infant's MN antigen status should be determined, because a negative direct Coombs' test may be found even when M antigen is present in the infant and hemolysis is occurring. Further studies are needed to determine the clinical impact of anti-M antibody on unrecognized hemolytic disease of the newborn.