Objectives - To determine the synovial mast cell response in early rheumatoid arthritis (RA) during clinical improvement, and to examine for relations with clinical and histological parameters of disease activity. Methods - Twenty two synovial samples were obtained from six patients with RA using needle arthroscopy. The mean disease duration at baseline was eight months, and two to three further samples were obtained over a mean follow up period of 15 months during which treatment initiated clinical improvement occurred. Sections were immunostained to detect MC1 and MC(TC) mast cells and correlations were sought between clinical and histological data. Results - The overall mean synovial mast cell density was 40.3 cells/mm2, with regional densities of 60.6 and 34.2 mast cells/mm2 in the superficial and deeper synovial layers respectively. The MC(T) subset predominated, outnumbering MC(TC) by 3:1. There was a significant correlation between the histological inflammation index and the MC(T) density, (r = 0.4, p < 0.05) but not the MC(TC) subset. The regional distribution and predominant subset of mast cells varied in individual patient's synovia over time, with a trend towards restriction of the mast cell response to the superficial synovium during clinical improvement. Conclusions - The mast cell response in early RA is characterised by substantial expansion of predominantly MC(T) mast cells that correlates with histological indices of inflammation. During clinical improvement, this expansion tended to become more superficial. Taken together with previous studies of long duration RA, which implicate MC(TC) cells in synovial damage and disease progression, these results suggest that MC(T) and MC(TC) mast cells may possess distinct functions in the spectrum of inflammatory events occurring during RA.