The objectives of this study were to (a) pilot test instruments measuring fatigue and quality of life (QOL); (b) pilot test an exercise intervention; and (c) estimate the effect size of this intervention relative to completion of combination therapy, fatigue, QOL, and walking distance in 20 patients with chronic hepatitis C about to begin interferon alpha and ribavirin treatment. Alpha reliabilities for both the Schwartz Cancer Fatigue Scale and Hepatitis Quality of Life Questionnaire were moderately high. Power analyses of all outcome measures indicated a small effect size and sample size estimate of 30–40 per group to achieve power of N.80. © 2009 Published by Elsevier Inc.