BACKGROUND On June 11th, 2009 the World Health Organization (WHO) declared the first influenza pandemic of the 21st century. Data regarding the clinical characteristics and course of this viral infectious disease are still being assessed. The aim of this study was to investigate and compare the possible differences in clinical course and outcome between H1N1-positive [H1N1(+)] and negative [H1N1(-)] patients. MATERIAL/METHODS This prospective study was conducted between July 2009 and January 2010 in a regional hospital in Greece. The study population consisted of 165 patients aged 14 years or older, with influenza-like illness (ILI) who, according to CDC recommendations, fulfilled the criteria for diagnostic influenza testing. Enrolled patients underwent a detailed diagnostic work-up. Infection by the H1N1 virus was diagnosed using real-time reverse transcriptase polymerase chain reaction, from pharyngeal swab specimens. RESULTS We identified 81 H1N1 (+) (49%) patients. Statistical analysis revealed that H1N1(+) patients were significantly younger (median age 27 vs. 35 years, p<0.05), had a decreased white blood cell count (median 7.200 vs. 8.415, p<0.05) and an increased percentage of monocytes (55.6% vs. 27.4%, p<0.05) compared to the H1N1(-) patients. The clinical presentation at the emergency department, as well as the hospital admission and disease complication rate, were not significantly different between the 2 groups. CONCLUSIONS The clinical characteristics of the new influenza virus appear to be mild and to resemble those of common influenza-like illnesses (ILI). The patients who tested positive for the H1N1 virus were younger and had an increased percentage of monocytes compared to the H1N1-negative patients.