The aim of the study was to reveal and investigate acute/recent HCV infection at the very early stage in seronegative blood donors and seronegative Injecting Drug Users (IDUs) and to assess clinical laboratory variants of infection, viral replication kinetic, disease outcome, host and viral characteristics. Two groups of patients were included in this study. The first group consisted of ELISA negative 7000 blood donors; the second group included 3000 Injecting Drug Users (IDUs). All patients were investigated on HCV RNA by qualitative PCR using mini pool method. A pool of 6 was applied for blood donors' and a pool of 5 for IDUs. PCR negative pools were excluded from the study, while PCR positives were examined on individual samples. Anti-HCV was detected by ELISA and RIBA. Detection HCV RNA was performed by Real time PCR technique using COBAS TaqMan Test. HCV genotyping--by INNO-Lipa. HLA typing--by Sequence Specific Primer Amplification (SSP). 16 patients with acute/recent HCV were revealed: 7 from blood donors, 9 from IDUs. Among them: 4 were symptomatics and 12 asymptomatics. Out of 4 symptomatics 3 were with jaundice. Among 12 asymptomatics: 8 had elevated ALT; 2 neither elevated ALT nor symptoms but developed anti-HCV; 2 were with normal ALT and without further anti-HCV seroconversion. Among 16 subjects: 9 had genotype -1b, 1--genotype 1a, 3--genotype 2a/2c and 3--genotype 3a. Out of 16 cases 4 cleared the virus; 12 developed chronic infection. Spontaneous clearance (recovery from the disease) was observed in 2 out of 4 symptomatic patients and only in 2 patients out of 12 asymptomatics. In all patients viremia increased rapidly and reached a peak by week 4. Viral titer was remarkably stable for the next three weeks, followed by two or three fold decrease by week 9. After week 10 the viremia rapidly decreased: 4 or 5 logs by week 12 and it became either undetectable by weeks 16-18 (viral clearance), or virus was not eliminated and viral titer persisted in all follow up period (chronic infection). HLA DRB1 1101, DQB1 0301 and DRB1 1301/DQA1 0103 alleles were associated with clearance of HCV whereas DRB1 0301 was associated with chronic infection. Prevalence of HCV among seronegative blood donors was 0.1% and among IDUs 0.3%. Among acute/recent HCV infected patients rate of chronicity was 75% (50% in symptomatics and 83% in asymptomatics). Rate of recovery was 50% in symptomatic patients and about 16% in asymptomatics. Acute/recent HCV infection might have following clinical laboratory forms: symptomatic disease with or without jaundice, asymptomatic with or without elevated ALT, but with further anti-HCV seroconversion. It remains unclear whether enigmatic form of disease--acute/recent HCV infection without further seroconversion exists or not.