In a recent study we found elevated thrombopoietin (TPO) levels along with a trend toward correlation between serum TPO and some acute phase reactants (APR) in patients with reactive thrombocytosis. In order to further clarify the behaviour of TPO in reactive conditions and to highlight the eventual drawbacks of serum TPO (sTPO) against plasma TPO (pTPO) measurements, serial measurements were made of sTPO, pTPO, interleukin (IL)-6, C-reactive protein (CRP), fibrinogen (FBG), and erythrocyte sedimentation rate (ESR) in 12 patients before and at the 3rd, 7th, 14th, 45th day after hip replacement surgery. Platelet count, sTPO and pTPO were also measured in 30 healthy donors. As expected sTPO were significantly higher than pTPO levels (approximately 30% on average) both in controls (P < 0.00001) and in patients (P < 0.00001). Overall a very good correlation (r = 0.975, P < 0.00001) was found between serum and plasma TPO, whereas no correlation was found between platelet count and the sTPO/pTPO ratio indicating that the difference between sTPO and pTPO is independent from platelet count. So both serum and plasma seem to be suitable samples for TPO measurement if it is taken into account that sTPO are about 30% higher than pTPO. All the parameters we measured in our patients increased during the post-surgery period and returned to the basal value at the 45th day. pTPO levels peaked at the 3rd day, preceding by 11 days the peak in platelet count. A significant correlation was found between pTPO and ESR (P = 0.012), pTPO and FBG (P = 0.044), pTPO and CRP (P = 0.033), and a nearly significant correlation between pTPO and IL-6 (P = 0. 054). These results indicate that, in the course of reactive conditions, an early rise in TPO precedes and probably induces a later increase in platelet count. Moreover, the significant correlations along with the similarity in the chronological variations between TPO and some APRs suggest that TPO behave like an APR.