alpha 1-Microglobulin (alpha 1-M), also called protein HC, is a low-molecular-weight (LMW) glycoprotein (about 30 kDa) with unique physicochemical properties. Using purified urinary alpha 1-M a standard and specific antibody against alpha 1-M, an assay system for alpha 1-M was developed, and the clinical significance of this protein was investigated by measuring total levels of alpha 1-M under physiological and pathological conditions. alpha 1-M is distributed in various body fluids: in serum, it consists mainly of free LMW alpha 1-M and monomeric IgA-alpha 1-M complex. The total alpha 1-M level in serum and urine usually reflects LMW alpha 1-M variation sensitively, and its determination is quite useful as an indicator of renal glomerulotubular dysfunction and hepatic dysfunction. Serum levels can vary, depending on IgA-alpha 1-M complex level, in parallel with the IgA concentration. The heterogeneity of alpha 1-M purified from different sources of urine by different procedures and underestimation of IgA-alpha 1-M complex by solid-phase antibody assays can be important causes for the discrepancy of serum levels between assays.