The capacity of normal and malignant human cells to synthesize β2-microglobulin has been studied in vitro. Quantitative determinations of β2-microglobulin by a radioimmunoassay were performed on culture media harvested from seven freshly explanted lymphoma cells and 37 cell lines of hematopoietic, mesenchymal, or epithelial origin. β2-Microglobulin was detected in all but one lymphoma cell culture. Lymphoma cells, freshly explanted, as well as those of continuously growing lines seem to have a low capacity to synthesize β2-microglobulin while permanent lymphoblastoid lines secrete the protein at approximately the same rate as mesenchymal cells. The highest production rate of β2-microglobulin was observed in some epithelial carcinoma cell lines. No correlation was found between the capacity to synthesize immunoglobulins and β2-microglobulin.