The study examined 60 HCV patients with normal baseline levels of TSH. The patients received subcutaneous pegylated interferon a-2b weekly in addition to oral ribavirin. Before the start of the interferon therapy, serum TSH, thyroglobulin-Ab (TG-Ab) and antiperoxidase antibodies (TPO-Ab) were measured. Three months after interferon therapy serum levels of TSH were measured to all patients; patients with abnormal TSH were subjected to the measurements of FT3, FT4, TPO-Ab, TG-Ab, and thyroid stimulating immunoglobulin levels (TSI). After 3 months of therapy, 48 patients (80%) had normal TSH, and 12 patients (20%) had abnormal TSH. Of 12 patients with abnormal TSH 10 (16.6%) had high levels of TSH (hypothyroidism), while the other two (3.4%) had low levels of TSH (Hyperthyroidism). Of 10 patients with hypothyroidisms, 6 patients (10%) had overt hypothyroidism and 4 patients (6.6%) had subclinical hypothyroidism. All patients with abnormal TSH had significant higher levels of TG-Ab, TPO-Ab and TSI (in cases with hyperthyroidism only) than the patients with normal levels of TSH (p < 0.001), the levels of TPO-Ab only of the most patients with abnormal TSH were above the normal reference range before the start of interferon therapy. Patients with hyperthyroidism, one was presented by clinical picture of overt hyperthyroidism, and the second by subclinical hyperthyroidism. All patients with overt hypo and hyperthyroidism received medical treatment, with normalization of levels of TSH and improvement of clinical symptoms and completed their course of interferon therapy Forty patients (66.6%) responded to interferon (-ve PCR for HCV), while 20 (33.3%) did not respond, 5 had TSH abnormalities that were significantly higher than those in patient with normal TSH {5/12 (41.6%).versus 15/48 (31%); p < 0.01}.