We report the case of a healthy woman (K.M.) who, after multiple pregnancies, developed an antibody directed against a nonpolymorphic region of the polymorphonuclear neutrophil (PMN) Fc gamma receptor III (FcRIII-CD16), which caused transient neonatal alloimmune neutropenia (NAIN). The antigenic target of the antibody was determined by an immunoprecipitation procedure and by phenotyping the mother's PMN. These latter did not react with monoclonal CD16 or polyclonal and monoclonal NA1 and NA2 antibodies, demonstrating the absence of PMN-FcRIII and, consequently, the NA-null phenotype. We also determined the frequency of the NA-null phenotype in a healthy, white population. Among 3,377 random blood donors, only four (in addition to K.M.) were PMN-FcRIII-deficient. These five individuals were healthy and only one (K.M.) presented an allo-CD16 antibody. The gene frequency of the NA-null phenotype was calculated as 0.0274 +/- 0.0059. We conclude that PMN-FcRIII deficiency is a rare phenomenon that can lead to CD16 alloimmunization and thus cause NAIN.