['To determine whether increased immunosuppression is a contributor to poor outcome in hepatitis C-infected orthotopic liver transplant (OLT) recipients, we retrospectively analyzed the consequences of using OKT3 in our program for steroid-resistant rejection (SRR).', 'We compared the histological recurrence of HCV in two contemporary cohorts of OLT recipients. Group 1 consisted of HCV-positive patients who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of age-, gender-, and initial immunosuppression-matched HCV-positive controls who were treated with at least one steroid pulse for acute cellular rejection but who did not require treatment with OKT3. Liver biopsies were obtained per protocol within the first month and as necessary to evaluate abnormalities in serum liver chemistries.', 'Mean and median follow-up were comparable for the two groups. Recurrence of HCV was diagnosed by histological verification and was documented in 16 of 19 (84.2%) group 1 patients versus 17 of 33 (51.5%) group 2 patients (p = 0.03). The interval to recurrence was significantly shorter in patients who received OKT3 (p = 0.028). Logistic regression identified OKT3 as a significant risk factor for the recurrence of HCV within the first year post-OLT (p = 0.0004). The histological severity score, based on the most recent liver biopsy at long-term follow-up or the explant biopsy if the patient required retransplantation, was significantly higher in group 1. Moreover, cirrhosis was demonstrable in a greater proportion of allografts in patients who had received OKT3 at some point (26.3% vs. 6%, p = 0.028). Long-term follow-up revealed a trend toward higher alanine aminotransferase levels (p = 0.05) and total bilirubin (p = 0.08) in group 1 patients.'] Is use of OKT3 associated with early and severe recurrence of hepatitis C after liver transplantation?