This study was performed in patients with hepatitis C virus (HCV) who were treated with hemodialysis to determine the relationships among alanine amino-transferase (ALT) levels, immunoglobulin (Ig) G anti-HCV, IgM anti-HCV core, and HCV RNA. Of 107 patients on hemodialysis, 27 had positive IgG anti-HCV. Eight of the patients who had HCV were evaluated every 8 months during a period of 2 years, using the following selection criteria: positive IgG against c-22, c33-c, 5-1-1, and c100-3 viral peptides; absence of infection by hepatitis A virus, hepatitis B virus, cytomegalo-virus, Epstein-Barr virus, herpes simplex virus, and human immunodeficiency virus, as well as absence of hepatotoxic drugs or cholelithiasis. We considered elevated ALT values as those more than 150% of the upper limit of normal. Three of the patients had persistent elevation of ALT levels, two had alternating elevation of ALT levels, and three had normal ALT levels in all blood samples. Of the 24 blood samples, 11 had elevation of ALT (45.8%) levels that showed positive IgM anti-HCV, but only 7 of these 11 had positive HCV RNA (63.6%). None of the 13 blood samples without elevation of ALT had positive IgM anti-HCV, but 5 had positive HCV RNA (38.5%). We found an excellent correlation between IgM anti-HCV and ALT levels (r = 0.81). There was no statistically significant difference between the mean ALT values on the 12 blood samples that had positive HCV RNA and the mean ALT values of the negative HCV RNA samples (53.5 +/- 28.0 IU/l vs. 37.4 +/- 17.5 IU/l, respectively). IgM anti-HCV is related to the elevation of ALT levels and can be used as a serologic marker to indicate the presence of active HCV induced liver damage. Serum ALT levels do not correlate with the detection of viral genome in sera. IgG anti-HCV is not necessarily associated with HCV RNA or IgM anti-HCV. The absence of IgM and HCV RNA in patients with IgG anti-HCV and normal ALT levels does not necessarily suggest the absence of active HCV infection.