A chemiluminescent test (CLT) which measures the metabolic response of human monocytes to sensitized red cells was developed to distinguish antibodies capable of causing the increased destruction of transfused incompatible red cells from antibodies which are clinically benign. Thirty sera containing IgG antibodies to high-frequency antigens were tested; 27 of these sera were also tested using the monocyte monolayer assay (MMA). The clinical significance of antibodies in 14 of the sera was known: three (anti-Ata (two), -JMH) caused accelerated clearance of 51Cr-labelled cells, five (anti-'MiIII', -Yta, three unidentified) caused haemolytic transfusion reactions and six (anti-Yta, -Ge, -JMH, -Xga, -Kna (two)) did not appear to affect red cell survival. Overall, results from the MMA and CLT showed good agreement; seven sera were negative in both assays, 18 sera were positive in both assays and two sera were positive in the MMA but negative in the CLT. There was no clear relationship between the activity of different antibodies and the level of sensitization as determined by flow cytometry. Antibody activity could be either increased or decreased by incubation of sensitized red cells with fresh serum. MMA results were in concordance with the clinical significance of antibodies where known in eight of 10 cases. CLT results were in concordance with clinical significance in 12 of 14 cases. Both assays gave false-positive results with serum from a patient with anti-Kna who had received red cell transfusions without adverse effect. This appeared to be due to the ability of anti-Kna to cross-link complement receptor 1 (CR1) on red cells to CR1 on monocytes; negative results were obtained using autologous monocytes.