The purpose of this study was to examine the time-course and relationships of technetium-99m (99mTc) neutrophils in muscle, interleukin-6 (IL-6), myosin heavy chain fragments (MHC), eccentric torque, and delayed onset muscle soreness (DOMS) following eccentric exercise in humans. Twelve male subjects completed a pre-test DOMS questionnaire, performed a strength test and had 100 ml blood withdrawn for analysis of plasma IL-6 and MHC content. The neutrophils were separated, labelled with 99mTc, and re-infused into the subjects immediately before the exercise. Following 300 eccentric repetitions of the right quadriceps muscles on an isokinetic dynamometer, the subjects had 10 ml of blood withdrawn with repeated the eccentric torque exercise tests and DOMS questionnaire at 0, 2, 4, 6, 20, 24, 48, 72 h, and 6 and 9 days. Bilateral images of the quadriceps muscles were taken at 2, 4, and 6 h. Computer analysis of regions of interest was used to determine the average count per pixel. The 99mTc neutrophils and IL-6 increased up to 6 h post-exercise (P < 0.05). The neutrophils were greater in the exercised muscle than the non-exercised muscle (P < 0.01). The DOMS was increased from 0 to 48 h, eccentric torque decreased from 2 to 24 h, and MHC peaked at 72 h post-exercise (P < 0.001). Significant relationships were found between IL-6 and 2 h and DOMS at 24 h post-exercise (r = 0.68) and assessment of the magnitude of change between IL-6 and MHC (r = 0.66). These findings suggest a relationship between damage to the contractile proteins and inflammation, and that DOMS is associated with inflammation but not with muscle damage.