In a review of the antenatal-postnatal records of 6062 patients attending the prenatal clinic at a large university perinatal center during 1980, 8.3% of the pregnant patients seen were Rho(D) negative and 91.7% were Rho(D) positive. Through routine antibody screening of all patients, 115 were found to have irregular antibodies which would otherwise not have been detected. Fifteen of these patients were Rho(D) negative, but they would have been included for antibody screening due to their Rho(D) negative status. Of the remaining 100 Rho(D) positive patients, clinically significant antibodies were observed in six patients; however, no maternal morbidity or hemolytic disease of the newborn was reported. Antecedent maternal risk factors for development of irregular antibodies were not sufficiently selective for predicting outcomes of such pregnancies. Furthermore, the only four patients with irregular antibodies requiring blood transfusion were cross-matched without difficulties. Findings suggest that screening all patients for irregular antibodies cannot be justified due to the prohibitive costs involved. However, because of the racially homogenous population studied, variations in the frequency of red blood cell genotypes between racial groups, and the irregular pattern of occurrence of irregular antibodies, the authors believe that further studies on the clinical impact and costeffectiveness of screening all antenatal patients for presence of irregular antibodies are necessary.