BACKGROUND: The objective of this study was to examine missed opportunities for participation in a prevention of mother-to-child transmission (PMTCT) programme in three sites in South Africa. A rapid anthropological assessment was used to collect in-depth data from 58 HIV-positive women who were enrolled in a larger cohort study to assess mother-to-child HIV transmission. Semi-structured interviews were conducted with the women in order to gain an understanding of their experiences of antenatal care and to identify missed opportunities for participation in PMTCT. RESULTS: 15 women actually missed their nevirapine not because of stigma and ignorance but because of health systems failures. Six were not tested for HIV during antenatal care. Two were tested but did not receive their results. Seven were tested and received their results, but did not receive nevirapine. Health Systems failure for these programme leakages ranged from non-availability of counselors, supplies such as HIV test kits, consent forms, health staff giving the women incorrect instructions about when to take the tablet and health staff not supplying the women with the tablet to take. CONCLUSION: HIV testing enables access to PMTCT interventions and should therefore be strengthened. The single dose nevirapine regimen is simple to implement but the all or nothing nature of the regimen may result in many missed opportunities. A short course dual or triple drug regimen could increase the effectiveness of PMTCT programmes.