OBJECTIVE: To identify regimen, individual, community and cultural factors that affect adoption and adherence to weekly vitamin A supplementation in Ghana. DESIGN: Fifty semi-structured interviews were conducted with women who would be eligible for vitamin A supplementation, 30 with husbands, and 13 with drug sellers, birth attendants and health workers. Six focus group discussions were also conducted with women. These interviews were followed by a 4-month capsule trial with 60 women. Data from a previously conducted communication channel survey of 332 women were also reviewed. SETTING: The study was conducted in Kintampo District in central Ghana. SUBJECTS: Participants for the semi-structured interviews and focus groups were selected from four villages and the district capital, and women in the capsule trial were selected at random from two villages. RESULTS: Knowledge of vitamins was low and taking 'medicines' for long periods and when healthy is a new concept. In spite of this, long-term supplementation will be accepted if motives are explained, specific questions answered and clear instructions are given. Potential barriers included the idea of 'doctor' medicines as curative, false expectations of the supplement, forgetting to take the supplement, losing the supplement, travelling, lack of motivation, perceived side-effects, concerns that the supplement is really family planning or will make delivery difficult, and concerns about taking the supplement with other 'doctor' or herbal medicine, or when pregnant or breast-feeding, or if childless. CONCLUSION: Successful supplementation programmes require appropriately designed information, education and communication strategies. Designing such strategies requires pre-programme formative research to uncover barriers and facilitators for supplementation.