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The clinical course of bacterial infectious diseases is often variable, especially in elderly patients. Thus, new biological markers have been sought to predict the disease outcome. Recent studies have revealed that Toll-like receptor (TLR) 2 and/or TLR4 on circulating monocytes are significantly up-regulated in bacterial infections. However, the lack of reliable quantification methods hampers extensive study on the modulation of these molecules in response to the patient's clinical condition. In this study, we developed a new quantitative flow cytometric analysis system for TLR2. We then carried out a longitudinal study on TLR2 expression levels on monocytes from patients suffering from bacterial infectious diseases during and after antibiotic treatment. The clinical outcome divided 37 patients into ‘cure’ ( n = 24) and ‘recurrence’ ( n = 13) groups. A significant difference between the two groups was recognized in the TLR2 levels just after antibiotic treatment (antibody-binding sites/cell, 4395 ± 784 versus 5794 ± 1484, P < 0·001). The risk of recurrence was associated significantly with TLR2 ( P < 0·001), but not C-reactive protein ( P = 0·351) levels assayed during the first remission. Furthermore, antibiotic effectiveness was associated inversely with TLR2 levels during antibiotic administration ( P < 0·001). Taken together, TLR2 expression levels on monocytes provide critical information for planning treatment against bacterial infectious diseases. [ABSTRACT FROM AUTHOR]