Several recent studies have indicated that patients infected with human immunodeficiency virus (HIV) exhibit a beneficial effect of co-infection with GB virus C (GBV-C). The benefit is demonstrated by slower progression to acquired immunodeficiency syndrome (AIDS) and prolonged survival time after the development of AIDS. In some but not all studies, a significant association between GBV-C/HIV co-infection and increased CD4+ cell counts has been reported. To understand further the possible role that GBV-C might play in the reduced morbidity and mortality among HIV-infected patients, we sought to examine the presence of different GBV-C genotypes in a cohort of co-infected patients. PCR products derived from the 5′-untranslated region (5′-UTR) and the second envelope gene (E2) were sequenced directly and genotyped by phylogenetic analysis. While 5′-UTR analysis delineated the major type, analysis of the complete E2 gene was required for identification of group 2 subtypes, designated 2a and 2b. Among 35 patients tested, GBV-C genotype was determined for 33: two patients were infected with genotype 1, 12 with type 2a, and 19 with type 2b. Clinical data were available for 25 genotyped patients: one infected with genotype 1, nine with genotype 2a, and 15 with type 2b. CD4 cell counts tended to be lower in patients infected with genotype 2a compared with those with genotype 2b (310 ± 136 vs 430 ± 199, P = 0.054). Additional studies with larger cohorts from separate geographical regions are needed to determine whether a particular GBV-C genotype is associated with reduced morbidity or mortality among HIV co-infected patients. J. Med. Virol. 70:141–149, 2003. © 2003 Wiley-Liss, Inc.