Loss of beta 2-microglobulin in human urine at near neutral pH is described. beta 2-Microglobulin was found to be unstable at pH 7.4 in 15 out of 70 specimens with bacterial infection. Breakdown of this protein was shown to be most active between pH 6.5 and 8.0 but some proteolysis also occurred between pH 5.0 and 6.0. Evidence that proteolysis of beta 2-microglobulin near neutral pH is due to neutrophil elastase-like activity was obtained by the following methods: use of the model elastase substrate L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide and the specific inhibitor 2-trifluoroacetylaminobenzenesulphonyl fluoride; use of neutrophil granule extracts and determination of the size distribution of beta 2-microglobulin proteolytic fragments. If increased numbers of pus cells are present, it is suggested that screening for elastase-like proteolysis should be undertaken before interpreting a measurement of beta 2-microglobulin.