The presence and kinetics of bone-resorbing activity in periapical lesions were studied with a rat model system. Lesions were found to expand most rapidly between induction on day 0 and day 15 ("active phase"), with enlargement occurring at a slower rate thereafter (days 20 and 30, "chronic phase"), as assessed by measurement of magnified radiographs and automated image analysis. Pooled extracts of periapical tissues obtained on day 15 contained significant levels of bone-resorbing activity, as determined by 45Ca release from pre-labeled fetal rat long bones. Normal rat dental pulp and periodontal ligament contained no activity. In two kinetic experiments, highest levels of bone-resorbing activity were detected in tissues on days 10 (10.4% and 11.6% specific 45Ca release/mg/mL) and 15 (8.9%). Activity declined thereafter on day 20 (4.4% and 6.1%) to near baseline levels by day 30 (1.4% and 3.3%). Identical levels of resorbing activity were found in the presence or absence of polymyxin-B, an inhibitor of bacterial lipopolysaccharide. These findings demonstrate that bone-resorbing activity is temporarily related to periapical bone destruction and suggest that this model may be useful for studies of mediators that are involved in the pathogenesis of inflammatory bone resorption.