Respiratory syncytial virus (RSV) infection of airway epithelial cells results in persistent NF-kappa B activation and NF-kappa B-mediated interleukin-8 production. Previous studies in airway epithelial cells demonstrated that tumor necrosis factor alpha (TNF-alpha)-induced NF-kappa B activation is transient due to regulation by I kappa B alpha. However, during RSV infection, I kappa B alpha has only a partial inhibitory effect on NF-kappa B activation. Studies presented here demonstrate that neither increased I kappa B alpha production which occurs as a result of RSV-induced NF-kappa B activation nor inhibition of proteasome-mediated I kappa B alpha degradation results in a reversal of RSV-induced NF-kappa B activation. Thus, while manipulation of I kappa B alpha results in reversal of TNF-alpha induced NF-kappa B activation, manipulation of I kappa B alpha does not result in a reversal of RSV-induced NF-kappa B activation.