1. We examined the factors which mediate the decrease of alkaline phosphatase (ALP) activity in human peridontal ligament (PDL) cells in response to cyclic tension-force. 2. ALP activity in human PDL cells obtained from three donors in response to cyclic tension-force (24% elongation) was 43% lower than that of the corresponding control. 3. ALP activity was decreased by the addition of conditioned medium obtained from the culture of the cells exposed to tension-force. 4. The inhibitory effect of the conditioned medium on ALP activity was partially abolished in the presence of indomethacin (10(-6) M) and IL-1 beta antibody (10 ng/well). Moreover it was almost completely abolished in the presence of both indomethacin and IL-1 beta antibody. 5. Treatment of PDL cells with exogenous PGE2 or IL-1 beta for 24 hr caused a dose-dependent decrease in ALP activity. Treatment with both PGE2 (10(-8) M) and IL-1 beta (1.25 x 10(-10) M) together decreased ALP activity by 47% compared with the non-treated control. 6. These findings suggest that ALP activity in PDL cells was decreased in response to the cyclic tension-force and that the decrease in ALP activity was mainly mediated by PGE2 and IL-1 beta produced by PDL cells in response to cyclic tension-force.