A 21-year-old woman with systemic lupus erythematosus (SLE) had meningismus, conjunctivitis, lymphadenopathy, and elevation of liver function values following ibuprofen therapy. All symptoms and laboratory value abnormalities resolved rapidly when the drug therapy was stopped. Two years later, a similar reaction occurred after taking tolmetin sodium. Fever, adenopathy, aseptic meningitis with a polymorphonuclear pleocytosis, and serum transaminase level elevations resolved rapidly after use of the drug was discontinued. The mechanism of this reaction to nonsteroidal antiinflammatory drugs in patients with SLE is not known.