The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethane diphosphonate (Cl2MDP) were evaluated in the rat adjuvant model of arthritis to directly compare their ability to inhibit arthritic processes. The results of the experiment indicated that both diphosphonates inhibited osseous changes, pedal inflammation, and the change in body weight gain patterns which are characteristic of this model. The latter effects suggest that diphosphonates may have antinflammatory activity that is not related to their previously known actions on bone. Cl2MDP appeared to be more effective than EHDP in this particular model when all aspects were considered. The relationship of these results to the potential safety of these compounds in clinical situations is discussed.