HIV infection has a major impact on the health of children in South Africa because the current prevention programs are ineffective. We evaluated the knowledge of prevention of mother to child transmission at a level-two hospital in the Free State Province of South Africa. A descriptive study was done using interviews of postpartum mothers during a 1-month period. Our results show a population vulnerable to the HIV epidemic, but with inadequate knowledge about perinatal HIV transmission. This implies that a more effective perinatal and especially postnatal antiretroviral regimen should be a priority for our health planners.