1. Activities of the three major classes of immunoglobulins were quantitatively determined in 481 sera from 106 patients with systemic lupus erythematosus residing in Mexico City and compared with activities in 112 healthy Mexico City residents. 2. To allow comparison with studies from other laboratories, results were related to a standard reference preparation from the World Health Organization and expressed in international units of immunoglobulin activity. 3. The mean activities of IgG and IgM, but not those of IgA, were significantly higher in the lupus sera than in controls. Abnormal elevation of IgG activity was related to the presence of antibodies to whole calf thymus nuclei, but not to those directed to nucleoprotein or DNA. Sera with rheumatoid factor activity had a higher mean IgA activity than those without it. 4. Patients with active lupus had significantly higher IgM activity than those with inactive disease. High IgM activities also correlated with presence of antibodies to calf thymus nuclei, nucleoprotein and native and heat-denatured DNA. 5. Abnormal elevation of the IgM activity without concurrent elevation of IgG or IgA activity was the most frequent pattern observed but was not predominant enough to be characteristic of systemic lupus.