Interleukin-6 (IL-6) is a pro-inflammatory cytokine commonly used in studies as a means of assessing chronic inflammatory status. Despite the use of plasma IL-6 as a marker of chronic inflammation few studies exist that examine the variability of plasma IL-6 within and between individuals. The purpose of this study was to assess inter- and intra-variability of plasma IL-6 concentration in men and postmenopausal women. Sixteen healthy postmenopausal women and 5 men completed the 2-week study. Fasted venous blood samples were obtained on three consecutive mornings for two consecutive weeks (six blood draws per participant). Mean plasma IL-6 values were 2.00+/-1.74 pg/mL. Intra-variability was not significantly different (p>0.05) however inter-variability was significantly different (p<0.05). The index of individuality (II) was 0.20 and the standard error of the mean (SEM) was determined to equal 0.16 pg/mL (0.32 pg/mL; 1.96 SEM). An II of 0.20 demonstrates the need to carefully evaluate changes in plasma IL-6 concentration instead of utilizing population-based reference norms. In an older adult population until plasma IL-6 differences exceed 0.32 pg/mL such values could be considered normal fluctuation between trials and most likely not attributable to a nutrition intervention.