This review seeks to describe data which support the concept that TNF alpha has a pivotal role in the pathogenesis of RA. There is now compelling evidence from in vitro studies and in animal models that this is the case. The in vitro studies suggest that the direct pathogenic effects of TNF alpha are amplified by its potential to act as a potent paracrine molecule, by inducing other pro-inflammatory molecules such as IL-1, and GM-CSF. It has yet to be established whether similar paracine effe...