In the 1980s he published an hypothesis for the mechanism of induction of autoimmune diseases, highlighting the role of cytokines. This model was validated in experiments with thyroid disease tissue. From 1984 he collaborated with Ravinder N. Maini at the Kennedy Institute of Rheumatology to study disease mechanism in rheumatoid arthritis, an autoimmune disease affecting 1% of the population.
Feldmann's group demonstrated that diseased joints have far more pro-inflammatory cytokines than normal, and postdoctoral researcher Fionula Brennan identified one of these, tumour necrosis factor alpha, (abbreviated TNFα) as the key.