In a population endemic for HTLV-I and hepatitis C virus (HCV), HTLV-I infection has been associated with a suppressed cell-mediated immunity measured by anergy to purified protein derivative (PPD). However, the effect of HCV and the impact of coinfection with HTLV-I and HCV have not been previously evaluated. To approach this issue, PPD reactivity was analyzed among 300 study subjects in the community-based Miyazaki Cohort Study. An erythema of <10 mm in diameter 48 hours after subcutaneous injection of the antigen defined PPD anergy. Logistic regression was used to estimate the relative risks. With adjustment for age, gender, and HTLV-I seropositivity, anti-HCV positivity was not independently associated with PPD anergy (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 0.6-1.9). Subjects with both anti-HCV and anti-HTLV-I had a fivefold risk of PPD anergy relative to those free of both infections (OR = 5.2; 95% CI = 1.9-13.8). The risk was nearly threefold among those with anti-HTLV alone (OR = 2.8; 95% CI = 1.4-5.3). Thus, coinfected study subjects were 1.9 times more likely to have PPD anergy compared with those singly infected with HTLV-I (p = .34). HCV infection may slightly increase the risk of PPD anergy among HTLV-I carriers.