To determine the seroprevalence of rubella virus infection among antenatal patients aged between 15 and 45 years in the Western Cape province of South Africa, in order to provide data to determine the need for vaccination to protect women of childbearing age. A cross-sectional study. Setting. Virology laboratory, Groote Schuur Hospital, National Health Laboratory Service (NHLS), South Africa. One thousand two hundred provincial serum specimens from participants in the 2003 Department of Health antenatal HIV/syphilis serosurvey were selected from the 4 districts of the Western Cape. The specimens were age-stratified and screened qualitatively for rubella immunoglobulin G (IgG) antibodies by means of a commercial immunoassay during October 2004. Within the Western Cape a total of 95.3% of women in the 15-24-year age group, 97.5% in the 25-34-year group and 98% in the 35-45-year age group were immune to rubella. There was no statistically significant difference in the rate of rubella susceptibility between the 4 districts tested. The study is an important step in addressing the seroprevalence of rubella infection in women of childbearing age in South Africa. Further information is needed on rubella seroprevalence from the other provinces in South Africa as well as formal implementation of rubella and congenital rubella syndrome surveillance to determine the feasibility of routine rubella immunisation.