BACKGROUND: In a few Caribbean islands, prevention of mother-to-child transmission (pMTCT) of HIV with zidovudine prophylaxis has reduced transmission rates from 27 - 44% to 5.5 - 9 %. OBJECTIVES: To highlight the uptake of interventions, preliminary outcomes and challenges in caring for HIV-exposed infants in a pMTCT HIVprogramme in a resource-limited setting. METHOD: A cohort of HIV-infected pregnant women were identified at the leading maternity centres in Greater Kingston through HIV counselling and testing and enrolled in the Kingston Paediatric and Perinatal HIV/AIDS Programme. Antiretroviralprophylaxis with zidovudine or nevirapine was given to the HIV-positive women and their newborns along with formula feeding. Some infants were enrolled retrospectively and followed irrespective of whether they had or had not received antiretroviral prophylaxis. A multidisciplinary team at the paediatric centres supervised protocol-driven management of the infants. Infants were followed for clinical progress and definitive HIV-infection status was to be confirmed at 18 months of age by ELISA or the Determine Rapid Test. RESULTS: During September 1, 2002 through August 31, 2003, 132 HIV-exposed infants were identified. For those infants prospectively enrolled (78), 97% received antiretroviral prophylaxis and 90% were not breastfed For all HIV-exposed children, 90% received cotrimoxazole prophylaxis and 88% continued follow-up care. Ninety-two per cent of all the infants remained asymptomatic and five died; of these deaths one is possibly HIV-related (severe sepsis at 11 weeks). This infant was retrospectively identified, had received no antiretroviral prophylaxis and was breastfed The main programme challenges, which were overcome, included the impact of stigma, compliance with antiretroviral chemoprophylaxis, breast-milk substitution and follow-up care. Financial constraints and laboratory quality assurance issues limited early diagnosis of HIV infection. CONCLUSION: Despite the challenges, the expected outcome is to prevent 50 new cases of HIV/AIDS in children living in Greater Kingston per year (300 over six years).