The aim of this study was to determine the variation in hepatitis C viral load over an extended period of patient follow up. Serum samples were collected from 49 female individuals who were identified as having been infected from the same source of hepatitis C-contaminated anti-D immunoglobulin during the period from 1977 (May) to 1978 (November), All patients attended the hepatitis C clinic at Cork University Hospital, Cork, Ireland. The study group was homogeneous with respect to gender, hepatitis C virus (HCV) genotype (Ib), and duration of infection. None of the patients had received antiviral therapy at the time of completion of study, Viral load quantifications were assessed using the Roche Monitor (F. Hoffmann-la Roche, Ltd., Basel, Switzerland) assay. The mean age of the study group at time of infection was 30.3 years (SD +/- 6.1) with a range from 18.5 to 43 years. The mean time of follow-up was 4.1 years (SD +/- 1.0) with a range from 1.2 to 5 years. The mean rate of change of viral load per year was 0.23 log(10) viral copies per mt serum for the study group (SD +/- 0.19) with a range of -0.18 to 0.78 that was significantly different from zero, P < 10(-10). The rate of change of viral load per year was negatively correlated with viral load at first determination, r=-.35, P=.01. Age at infection did not correlate with the slope of change of viral load, P=.10, In conclusion, most women infected with HCV Ib will have an increase in viral load over time but a few patients who acquire infection early in adult life will show a decrease in viral load.