OBJECTIVE To evaluate the effects of radiation synovectomy (RSYN) with holmium-166 ferric hydroxide macroaggregate (Ho-166 FHMA) on synovium and synovial fluid in normal metacarpo- and metatarsophalangeal joints of horses and to determine intraarticular distribution of radioactivity after Ho-166 FHMA treatment. METHODS Either Ho-166 FHMA or nonradioactive Ho-165 FHMA was injected into metacarpo- or metatarsophalangeal joints. METHODS Six adult mixed-breed horses without any clinical evidence of metacarpo- or metatarsophalangeal joint disease. METHODS Joints were injected with a single high dose of Ho-166 FHMA (mean, 1,000 MBq/joint) or a nonradioactive Ho-165 FHMA preparation (controls). Clinical examination, arthroscopy, synovial fluid analyses, and histologic studies were performed to detect effects of RSYN. Scintigraphy was used to localize intraarticular distribution of Ho-166 FHMA. RESULTS Ho-166 FHMA treatment induced joint inflammation leading to regional edema, effusion, and scar tissue formation. Scintigraphy revealed the highest intensity of radioactivity in the proximal plantar joint pouch, at which the Ho-166 FHMA treatment caused multifocal necrosis. In the dorsal joint pouch, however, arthroscopic study and histologic analysis showed very little effect of RSYN. There was no regeneration of synovium evident within 2 months. Synovial fluid protein concentration was significantly (P <.01) elevated, and some residual radioactivity remained for 5 days after Ho-166 FHMA injection. CONCLUSIONS Injection of a single high dose of Ho-166 FHMA caused multifocal necrosis of synovium and deep, soft-tissue injury in equine fetlock joints. CONCLUSIONS Inflamed equine joints with synovial lining hyperplasia could benefit from Ho-166 FHMA-induced radiation synovectomy if excessive scar tissue formation can be avoided.