To determine the current frequency of red blood cell antigen alloimmunizations that are capable of causing hemolytic disease and would be suitable for prenatal DNA studies. We reviewed blood-bank records at a single large tertiary center to identify patients with a positive antibody screen between January 1993 and June 1995. Data were analyzed based on age, gender, and specific blood-group alloimmunizations. The incidence of antibodies as published in the literature was reviewed and compared with our data. We identified 452 women who had a positive antibody screen. The frequencies of specific alloimmunization relevant to the development of fetal hemolytic disease were: anti-D, 18.4%; anti-E, 14%; anti-c, 5.8%; anti-C, 4.7%; Kell group, 22%; anti-MNS, 4.7%; anti-Fya (Duffy), 5.4%; and anti-Jka, 1.5%. Compared with other populations, in our group the frequency of antibodies to RhD decreased and Kell alloimmunization increased between 1967 and 1996. Despite the use of rhesus immune globulin, anti-D is still a common antibody identified in women presenting to a tertiary care center. The frequency of the Kell-group alloimmunization is higher among the central New York female population than in other populations. Rhesus and Kell antigen status can be determined by DNA studies. Research in prenatal determination of fetal antigen status should continue, as alloimmunization to these antigens is common.