β2-Microglobulin has been solubilized from human blood cells by sonication, deoxycholate treatment, or acidification. The average number of β2-microglobulin molecules per cell, measured after acidification, was 0.54 × 105 for platelets, 18 × 105 for mononuclear cells, and 6.9 × 105 for polymorphonuclear cells. No β2-microglobulin was detected in red blood cells. A relatively large proportion of the protein in platelets and mononuclear cells was located on the cell surface as compared with polymorphonuclear cells, according to experiments performed with 125I-labeled rabbit anti-β2-microglobulin IgG.