I n this study we describe, to our knowledge, the first experiment using the microdialysis technique for studying the release of prostaglandin E2 (PGE2) in the proximal tibia metaphysis secondary to mechanical loading. Nine healthy females, six in the loading group and three controls, mean age 34+/-2 (years+/-SEM), participated. A standard microdialysis catheter was inserted into the tibia metaphyseal bone under local anesthesia. Samplings were done every 15 min under a 2-h equilibration period. Thereafter, heel-drops (one impact per second) with as hard impact of the heels into the floor as possible, were done for 5 min by the subjects in the loading group. The control group performed no exercise. Sampling continued after this for another 2-h period. Basal levels of PGE2 in the proximal tibial metaphysis were determined to a mean of 45+/-10 pg/ml (mean+/-SEM, n = 6). The major finding was a 2.5-3.5-fold increase in the release of PGE2 after mechanical loading. The increase was statistically significant (P < 0.05 compared with basal levels) 1 h after the mechanical loading and persisted for the rest of the experimental period. No major alterations were observed in the control group. In conclusion, our data demonstrate that in situ microdialysis is a useful method for studying the PGE2 production in human bone. Furthermore, a rapid and significant increase in PGE2 levels was noticed in response to dynamic mechanical loading.