A few studies in patients with reactive thrombocytosis identified levels of the hormone higher than expected, and suggested that TPO behaves as an acute-phase protein and was responsible for increased platelet count. At the opposite, other studies did not find any significant rise of the hormone in patients who similarly developed reactive thrombocytosis. To gain further information on this topic, we compared TPO levels and platelet counts in two series of patients hospitalized for acute illnesses: one with strong elevation of both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and the other with normal values. Within the group of subjects with high ESR and CRP, 38 had normal platelet counts, while 15 had thrombocytosis. No thrombocytosis was observed in control patients. Patients with high acute phase indexes had significantly higher TPO levels and platelet counts than control patients. We identified significant positive correlations between ESR and CRP, and between TPO and CRP. Interestingly, no significant relationship between platelet counts and TPO levels was find. When we grouped patients with acute-phase reaction according to absence or presence of thrombocytosis, we found similar TPO values. Conversely, positive correlations between platelet count and IL-6 and between TPO and IL-6 have been identified. All together our results confirm that TPO acts as an acute phase protein but exclude the possibility that it is uniquely responsible for thrombocytosis of inflammatory disorders, which might recognize in IL-6 a credible candidate as a cooperating factor.