Two forms of tartrate-resistant acid phosphatase (TRACP) circulate in human blood, TRACP 5a derived from inflammatory macrophages and TRACP 5b derived from osteoclasts. We compared the clinical performance of the following TRACP immunoassays for monitoring alendronate treatment in postmenopausal women: 1) TRACP 5b activity using a selective pH; 2) TRACP 5b activity using a selective substrate; 3) Total TRACP activity; 4) Total TRACP protein amount; 5) TRACP 5a activity; 6) TRACP 5a protein amount. TRACP and other bone turnover markers were measured before the start of treatment and at 3 months. Alendronate treatment decreased TRACP values determined with assays 1, 2 and 3, and had no effect on the values determined with assays 4, 5 and 6. Clinical performance of assays 1, 2 and 3 was good, and these assays correlated with each other and with the other bone markers. This study showed that TRACP 5b specific methods are useful for monitoring changes in bone resorption during alendronate treatment, and alendronate treatment does not affect serum TRACP 5a levels.