Bisphosphonates suppress bone destruction in various diseases. We studied the effects of 3-amino-hydroxypropylidene-1,1-bisphosphonate (APD), and dimethyl-APD in the collagen model of chronic arthritis in rats. The incidence and severity of arthritis was not lower in rats treated with APD or dimethyl-APD compared with controls. The cellular and humoral immune responses to collagen were also similar in the treated and untreated animals. In all animal groups the same bone destruction was found radiographically 42 days after immunization. This study demonstrates that bisphosphonates do not suppress the course of collagen arthritis in rats.