In this study we investigated the activation of nuclear factor-kappaB in the carrageenin-induced rat pleurisy. We found that nuclear factor-kappaB DNA binding activity, measured in inflammatory cells which migrated into the pleural cavity, was detectable at 3 and 6 h, markedly increased at 24 h and decreased at 48 h after induction of the inflammation. The increase in nuclear factor-kappaB DNA binding activity paralleled both exudate formation and leukocyte infiltration. Treatment of animals with pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappaB activation, inhibited the nuclear factor-kappaB DNA binding activity as well as exudate formation and leukocyte infiltration. These results indicate that nuclear factor-kappaB is activated in the carrageenin-induced pleurisy and suggest that its inhibition may represent a novel strategy for the modulation of inflammatory response.