Clinical significance of TT virus (TTV) infection was investigated in Egyptian patients with chronic liver disease and volunteer blood donors by a cross sectional analysis. TTV DNA in serum was assessed by a semi-nested polymerase chain reaction. The prevalence of TTV DNA did not differ among patients with chronic hepatitis B (11/24, 46%), chronic hepatitis C (22/72, 31%), or schistosomal liver disease (14/39, 36%). No difference in prevalence was found between blood donors (32/109, 29%) and each of the patient groups. Clinical background including mean age, sex distribution, history of blood transfusion, and mean level of alanine aminotransferase did not differ between TTV DNApositive and -negative individuals in any of the study groups. Ultrasonographic evidence of liver cirrhosis was similar between TTV-positive and -negative patients in each of the chronic liver disease groups. TTV infection was not associated with hepatitis B or C virus infection in blood donors. The only significant difference observed was the lower concentration of serum HCV RNA in TTV DNA positive compared with negative patients with chronic hepatitis C (3.0 Β± 1.4 vs. 4.0 Β± 0.9 log copies/ml, P < .001). In conclusion, TTV infection was not associated with either past history of blood exposure or infection with bloodborne hepatitis viruses in Egypt. No clinical significance of TTV was found in the present study. However, a reciprocal interaction was suggested between TTV and HCV replication.