Little is known about the effects of eccentric exercise on several oxidative stress-sensitive signalling pathways which mediate the expression of genes involved in the inflammatory response. We have investigated changes in NF-kB activation induced in peripheral blood mononuclear cells (PBMC) by acute eccentric exercise and by submaximal eccentric training. Subjects, aged 18-24 years carried out two bouts of eccentric exercise separated by six weeks of training. Soreness, vertical jump height and plasma creatine kinase were significantly modified following the first bout. NF-kB activation, p50 and p65, phospho-IkBa and phospho-IKK protein level increased in PBMC, while IkBa protein level was significantly reduced. Changes were significantly attenuated following the second exercise bout. When elderly subjects, aged 66-75 years, performed a similar protocol of exercise, activation in the NF-kB pathway induced by a first bout of acute exercise was accompanied by a significant increase in iNOS, COX-2 and IL-6 mRNA level and protein content, and changes were also attenuated following a second bout after training. Animal experiments confirmed by CHIP-assay that transcription of NOs isoforms in muscle was directly regulated through binding of NF-kB to the corresponding gene promotors, and that this effect was prevented by training. Data obtained indicate that, both in young and elderly individuals, regular eccentric training might be an effective method of preventing undesirable inflammatory responses induced by eccentric exercise.