We prospectively studied the value of measuring C-reactive protein (CRP) levels in patients with systemic lupus erythematosus (SLE) to distinguish between disease exacerbation and infection. During a 2 year followup of 71 lupus patients, 38 episodes of disease exacerbation and 36 episodes of infection could be analyzed. Plasma samples were obtained at least once a month. CRP levels were increased (greater than 6 mg/l) during 25 of the 38 exacerbations and during 32 of the 36 infections. Median CRP levels during infection (60 mg/l; range 1-400) were higher than during disease exacerbation (16.5 mg/l; range 1-375) (p less than 0.05). Levels of CRP rose prior to the exacerbation (p less than or equal to 0.01) and fell afterwards (p less than or equal to 0.01). During exacerbations accompanied by serositis, median levels of CRP (76 mg/l; range 2-375) were higher than during exacerbations without serositis (16 mg/l; range 1-53) (p less than 0.02). CRP levels exceeding 60 mg/l during exacerbations without serositis indicated infection in all cases. Thus, measurement of CRP in SLE is valuable to distinguish between infection and exacerbation only in the absence of serositis.