Of 46 patients with clinical melioidosis, 35 (22 culture-positive and 13 culture-negative) had relatively uneventful disease courses, with elevated serum C-reactive protein (CRP) concentrations (greater than 5 mg/dl) that decreased with the commencement of appropriate antibiotic therapy, and continued to show an uninterrupted decrease (mean 29.4 days, range 12-52 days) to the normal range (less than 1 mg/dl), with resolution of their infections. In five culture-positive patients with complicated disease courses, CRP concentrations remained elevated (greater than 5 mg/dl) until the underlying disorders were successfully managed, or until the antibiotic regimen was changed, and CRP values then decreased to the normal range. During surveillance, elevated CRP concentrations (greater than 10 mg/dl) led to the diagnosis of reactivation of infection in three afebrile patients, while the serum CRP values in other patients remained within the normal range in the absence of intercurrent complications. The CRP estimations may be helpful in ascertaining active infection in patients with low serum levels of specific IgM antibody, and serial measurements of serum CRP in patients with clinical melioidosis may be useful in determining the optimal duration of treatment and for detecting occult or unresolved infection with Pseudomonas pseudomallei.