Heterosexual transmission of hepatitis C virus (HCV) is uncommon, with few studies undertaken in Central Africa. To determine the frequency of inter-spouse HCV transmission, cross-sectional studies of elderly individuals in Ebolowa, Cameroon and Nola, Central African Republic, in which, respectively, 24 and 83 long-term couples had been identified, were examined further. Blood samples were tested for antibody to HCV. Anti-HCV positive samples were genotyped by phylogenetic analysis of a fragment of the NS5B gene. In Nola, 4 out of 9 (44.4%) wives of anti-HCV positive husbands and 1 out of 74 (1.4%) wives of anti-HCV negative husbands were anti-HCV positive (P < 0.001); in Ebolowa, the corresponding proportions were 10 out of 15 (66.7%) and 3 out of 9 (33.3%) (P = 0.21). After adjustment for age and site-specific risk factors of HCV infection, HCV seropositivity of the wives remained associated with their husbands' HCV serostatus, significantly so in Nola (P = 0.003) and marginally in Ebolowa (P = 0.06). In 7 out of 14 concordant seropositive couples, the genotype could be determined in both spouses. Four couples were infected with different genotypes, while three were infected with the same genotype. Thus, serological concordance between the spouses was related to a combination of infections acquired independently and inter-spouse transmission. It could not be determined whether inter-spouse transmission occurred sexually, through blood–blood contact, or otherwise. Inter-spouse transmission may have contributed to the high prevalence among elderly populations of Central Africa since some patients infected during healthcare subsequently transmitted the virus to their spouse. J. Med. Virol. 83:2113–2118, 2011. © 2011 Wiley Periodicals, Inc.