Simultaneous visualization of nerves and mast cells in the rat synovium was possible with double staining. Thus, a direct comparison could be made of nerves and mast cells in the ankle joints of healthy rats and in those with severe adjuvant induced polyarthritis. Nerves were studied with avidin-biotin-peroxidase complex (ABC) immunostaining, using heterologous antisera to protein gene product 9.5 (PGP 9.5), a recently discovered neural protein, and the neuropeptides substance P and calcitonin gene related peptide (CGRP). Mast cells were visualized by metachromatic staining of granule heparin. With double staining of sections, a parallel distribution of mast cells and nerves in all parts of the normal synovium was noted. In rats with adjuvant induced arthritis, a near total parallel disappearance of mast cells and nerves in the synovium occurred. In the arthritic rat such mast cell/nerve "units" were only present in the region where synovium attaches to bone. The observed regional depletion of both nerves and mast cells in arthritis may be of importance in the pathophysiology of arthritis.