Objective: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. Methods: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiarycare hospitals was conducted. Results: The mean age of the patients was 42 +/- 17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37 +/- 23 days) was significantly longer compared to the patients with ID (25 +/- 12 days) (p = 0.007). In patients with MD, the mean duration of fever (51 +/- 35 days) was longer compared to patients with ID (37 +/- 38 days) (p = 0.052). Conclusions: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies. (C) 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.