Effects of the analog (STA2) of thromboxane A2 (TXA2) and the analog (OP41483) of prostacyclin (PGI2) on bone resorption were studied in vitro in comparison with that of prostaglandin E2 (PGE2). STA2 and OP41483 are analogs of TXA2 and PGI2, respectively, and are chemically stable. In measuring the release of 45Ca under culture, using 45Ca previously incorporated in neonatal mouse calvaria as an indicator, an increase in the release of 45Ca was observed only at high doses such as 10-5 M and 10-4 M of both STA2 and OP41483. This bears a close resemblance to the resorptive conditions in the concentration range of PGE2, known as a strong bone resorptive factor, from 10-8 M to 10-5 M. PGE22, STA2 and OP41483 all have a resorption potency ratio of approximately 100 : 3 : 1. A time-course study followed for observing the activities responsible for bone resorption of these three reagents at 6, 24, 48 and 72 h. Each of the reagents used showed a lineal increase with the passage of time. In the experiment in measuring adenosine 3′, 5′ monophosphate (cyclic AMP), the culturing time was limited to 10 min because of its activity time being very short and the reagents (PGE2, STA2 and OP41483) in a concentration 10 times as high as that of those used in other five experiments were used. As a result, it was indicated that the cyclic AMP production level of PGE2, STA2 and OP41483 was almost the same, but was significantly high as compared with that of the group of controls (no reagent added), though it did not reach that of parathyroid hormone (PTH). Imidazole known as a blocker to thromboxane synthesis has an inhibitory effect on both basal bone resorption and PTH-induced bone resorption, but the addition of STA2 and OP41483 resulted in overcoming the inhibitory effect of this substance and producing an effect on bone resorption. This phenomenon was almost similar to the effect produced when PGE2 was added. Researching the inhibitory effect on resorption of calcitonin (CT) demonstrated that it inhibits not only the resorption of basal bone, but also the bone resorption induced by STA2, OP 41483, or PGE2. The above data suggest the TXA2 and PGI2 may be responsible for bone resorption and similar in mechanism to PGE2.