UNLABELLED: OBJECTIVES; To synthesise data from four recent studies in Tanzania examining maternal syphilis screening and its operational implementation in routine antenatal clinics (ANC), drawing lessons for strengthened antenatal services for the prevention of mother-to-child transmission (PMTCT) of HIV. METHODS: The impact of untreated maternal syphilis was examined in a retrospective cohort of 380 Tanzanian women. Effectiveness and cost-effectiveness of screening and single dose benzathine penicillin treatment were prospectively examined in 1688 pregnant women. Observation, interviews and facility audits were carried out in health facilities within nine districts to determine the operational reality of syphilis screening. RESULTS: Overall, 49% of women with untreated high titre syphilis experienced an adverse pregnancy outcome compared with 11% of uninfected women. Stillbirth and low birthweight rates among those treated for high- or low-titre syphilis were reduced to rates similar to those for uninfected women. The economic cost was $1.44 per woman screened and $10.56 per disability-adjusted life year saved. In the operational study, only 43% of 2256 ANC attenders observed were screened and only 61% of seroreactive women and 37% of their partners were treated. Adequate training, continuity of supplies, supervision and quality control are critical elements for strengthened antenatal services, but are frequently overlooked. CONCLUSIONS: Maternal syphilis has a severe impact on pregnancy outcome. Same-day screening and treatment strategies are clinically effective and highly cost-effective, but there are significant challenges to implementing syphilis screening programmes in sub-Saharan Africa. Current PMTCT interventions present an opportunity to reinforce and improve syphilis screening. Increasing PMTCT coverage will involve similar operational challenges to those faced by syphilis screening programmes.