Nearly 30% of pregnant women in South Africa are estimated to be HIV seropositive, yet adherence to guidelines for the prevention of mother-to-child transmission of HIV (PMTCT) is often low. A pilot study was developed to see whether PMTCT services provided by the South African Government could be enhanced by the Mamekhaya program, a combination of the mothers2mothers peer-mentoring program and a culturally adapted cognitive-behavioral intervention (CBI) from the USA. Pregnant women attending two maternity clinics offering PMTCT in Gugulethu and Vanguard Townships, Cape Town, South Africa, were invited to participate in the study. Women at the intervention site (Gugulethu) received the support of a mentor mother and also attended an eight-session Mamekhaya CBI. At the control site (Vanguard), women received standard services provided by midwives and counselors. Baseline assessments were completed by all participants at enrollment (n=160), and follow-ups were completed six months later by 44% of participants. Self-reports of adherence to PMTCT practices were high across both sites (90% or more engaging in the core practices). Women at the Mamekhaya site showed significantly greater improvement in establishing social support and reducing depression scores than women at the control site. Mamekhaya participants also showed trends for better attendance at follow-up medical visits, and greater improvements in positive coping. The greatest effect of the Mamekhaya program was to increase HIV knowledge scores, particularly with regard to understanding the meaning and importance of viral load and CD4 test results. Results from this pilot study show promise that augmenting basic PMTCT services with mentor mothers and a culturally adapted CBI can be effective in conveying information and in improving the emotional outlook and hopefulness of HIV-positive pregnant women in South Africa.