β2-microglobuIin (β2m) is a small protein that forms the light chain of the class I major histocompatibility molecule and is also present in soluble form in serum and cerebrospinal fluid (CSF). Measles is associated with immune activation and evidence of immunologic abnormalities that persist for several weeks. To assess further the immunologic changes occurring during measles, β2m was measured in plasma and CSF. β2m became elevated during measles before the onset of the rash and was highest during the rash. Elevations persisted for several weeks and correlated well with levels of soluble interleukin-2 receptor and neopterin and less well with soluble CD8. CSF β2m was elevated in postmeasles encephalomyelitis. Plasma levels of β2m did not correlate with spontaneous proliferation of peripheral blood mononuclear cells (PBMC) or with in vitro production of β2m by cultured PBMC. The data suggest that increases in β2m in measles correlate better with cytokine production than with cell proliferation. © 1992 The University of Chicago.