In this sensitive radioimmunoassay for beta 2-microglobulin (beta 2-M) involving a commercially available monoclonal antibody, we used a second monoclonal antibody, produced in our laboratory, for affinity-chromatographic purification of beta 2-M. Both monoclonal antibodies bound to all of the charge isomers of beta 2-M identified by two-dimensional gel electrophoresis. Polyethylene glycol was used to separate the phases after incubation for 3 h at room temperature. Sensitivity was 0.25 ng of beta 2-M. Within-assay CVs were less than 5.4%, between-assay CVs less than 7.3%. Analytical recovery was 95-102%. The reference interval was 1.2-2.2 mg/L for 49 healthy subjects. The correlation coefficient for comparison with a polyclonal antibody assay was 0.997 for 44 patients. In a study correlating serum beta 2-M and creatinine concentrations with glomerular filtration rate for 50 patients, correlation coefficients for log-log transformed data were -0.94 and- 0.95, respectively. Concentrations of beta 2-M were increased in serum of patients with imparied renal function and also in patients with normal renal function who had disorders involving the immunologic response. We found no clear-cut advantage of measuring serum beta 2-M over serum creatinine in the estimation of glomerular filtration rate.