One suggested cause of the high turnover osteopenia of experimental inflammatory arthritis is disuse of affected joints. To compare the influence of immobilization or disuse, or both, with that of inflammatory arthritis on bone turnover, rabbits were placed into four groups. In group 1, arthritis was induced in the right knee by seven intra-articular injections of 1% carrageenan, over 49 days; in group 2, a plaster cast was applied to immobilize the right hindlimb in flexion; in group 3, arthritis was induced and the hindlimb was immobilized; and in group 4, nothing was done (control). The fluorescent label calcein was administered in drinking water (0.05%) ad libitum to all groups on days 22-36. On day 49, specimens were prepared for analysis of bone volume and new bone volume at a near site (right femur) and at remote sites (contralateral femur and ipsilateral humerus). The data were analysed by multiple regression and Bonferroni tests. In group 1, new bone volume was three times higher than in group 2 or 4 (p < 0.05 for each comparison); this indicated increased bone remodeling in the right femur. This contrasted with group 2, in which neither index of bone remodeling was changed. The combination of immobilization with arthritis resulted in more intense osseous effects of inflammatory arthritis, with a one-quarter decrease in bone volume (group 3, 30.99 +/- 2.50; group 4, 42.07 +/- 2.38, p < 0.05), as well as a 4-fold increase in new bone volume (p < 0.001) compared with group 1.(ABSTRACT TRUNCATED AT 250 WORDS)