The diagnosis of systemic lupus erythematosus (SLE) often depens on positive tests for antinuclear antibody, LE cells, and antibody to DNA. In fact, the presence of such serological markers is virtually required for the diagnosis of active disease. This report describes 5 well-studied patients with SLE who initially presented with negative serology despite active multisystemic disease. When followed from 10 months to 7 yr, negative serologic markers, including the ANA, LE cell test, and anti-DNA were seen to change from negative to positive, analogous to the seronegative rheumatoid patient who may become seropositive. In a few cases of lupus, therefore, negative serologic tests do not always exclude SLE, and serial testing at periodic intervals may be indicated.