Nine untrained men (22-29 yr) performed 45 min of downhill running (16% incline, 70% of maximum heart rate). Needle biopsies of the vastus lateralis were performed before, 45 min after, and 5 days after exercise. Immunohistochemical staining of muscle cross sections revealed a 135% increase in muscle interleukin-1β (IL-1β) immediately after and a 250% increase (P < 0.03) 5 days after exercise. Using a rating scale (0-3) for the presence of neutrophils, light microscopic examination showed a significant accumulation of neutrophils in muscle biopsies taken 45 min after and 5 days after exercise [before: 0.5 ± 0.2, 45 min after: 1.5 ± 0.3 (P < 0.01), and 5 days after: 1.2 ± 0.2 (P < 0.04)]. In addition, electron microscopic analysis showed an increase in the percentage of damaged Z-bands relative to total Z-bands [before: 4.8 ± 3.5%, 45 min after: 32.5 ± 8.6% (P < 0.05), and 5 days after: 14.1 ± 3.2%]. Neutrophil accumulation was positively correlated to intracellular Z-band damage (ρ = 0.66, P < 0.001). Immunohistochemical staining for IL-1β was related to neutrophil accumulation in muscle (ρ = 0.38, P < 0.06) and to plasma creatine kinase levels (ρ = 0.416, P < 0.04). These data indicate that after eccentric exercise ultrastructural damage to skeletal muscle is associated with neutrophil infiltration and muscle IL-1β accumulation.