We examined the time course of the development of hemorrhagic synovitis in response to repeated autologous blood injections into knee joints in mature dogs and the possible usefulness of joint imaging with technetium-99m pyrophosphate (Tc99m-PYP) in monitoring the early response of synovium to blood. Experimental hemarthrosis was induced in dogs by twice weekly injection of autologous blood into the knee joints. Sequential examination of the synovium at monthly intervals over a period of 12 weeks revealed early inflammatory cell infiltration and capillary neovascularization with eventual replacement of the normal fatty synovium by dense fibrous tissue. Serial Tc99m-PYP joint images demonstrated a progressive increase in isotope accumulation in the knees during the course of the study. Further isotope accumulation was observed after CO2 laser synovectomy. During the 24-week course of the entire study, no changes in joint cartilage or bone were observed by gross inspection or radiologic and light-microscopic examination. The findings indicate that the progressive proliferative, inflammatory, fibrotic changes in joint synovium associated with experimental hemarthrosis in dogs may be noninvasively and semiquantitatively assessed with the use of Tc99m-PYP scintigraphy. Evidence is also presented that the intensity of Tc99m-PYP joint accumulation (immediate static images) may not readily reflect synovial vascularity or synovial tissue mass.