Sera from 70 patients on maintenance haemodialysis, 98 patients with chronic liver disease, and 232 volunteer blood donors in the province of KwaZulu Natal, South Africa, were screened for GB virus/hepatitis G virus (GBV-C/HGV) RNA and anti-E2 by reverse transcription-polymerase chain reaction (RT-PCR) and by an enzyme-linked immunosorbent assay (ELISA), respectively. GBV-C/HGV RNA was detected in 17/70 (24.3%) haemodialysis patients, 12/98 (12.2%) patients with chronic liver disease, and 44/232 (18.9%) blood donors (Africans [29/76; 38.2%]; Asians [2/52; 3.8%]; Whites [11/49; 22.4%], and "Coloureds" [persons of mixed origin; 2/55; 3.6%]). Overall (anti-E2 and/or RNA) 43.9% (43/98) of patients with chronic liver disease, 47.1% (33/70) of haemodialysis patients, and 31.9% (74/232) of blood donors (Africans [44/76; 5.9%]; Asians [5/52; 9.6%]; Whites [15/49; 30.6%], and Coloureds [9/54; 16.6%]) were exposed to GBV-C/HGV infection. There was a significant difference in the prevalence of GBV-C/HGV infection (RNA and/or anti-E2) between African blood donors and the other racial groups (P < .001), and between blood donors and haemodialysis patients (P = .02) and patients with chronic liver disease (P = .04). Anti-E2 antibodies and GBV-C/HGV RNA were almost mutually exclusive. GBV-C/HGV-infected haemodialysis patients received more transfusions (P = .03) than noninfected patients. There was no significant difference in liver biochemistry between GBV-C/HGV-infected and noninfected patients and between blood donors in each of the four racial groups. The high prevalence of GBV-C/HGV infection in blood donors and chronic liver disease patients, and the lack of elevated liver enzymes and clinical hepatitis in blood donors and haemodialysis patients, suggest that GBV-C/HGV may not be associated with liver disease.