STUDY OBJECTIVE Down syndrome (DS), the commonest cause of congenital developmental disability in developed countries, has only recently been shown to have an incidence in black South African neonates as high, and in some studies higher, than currently seen in First-World nations. It has also been reported that the mothers of black African DS newborns and medical and nursing staff have difficulty recognising and diagnosing DS in black neonates. The aims of this study were to document the clinical features of black DS infants and children, compare these to the features of previously documented DS infants and children from other ethnic groups, and finally to ascertain if and for how long the difficulties recorded in diagnosing DS in blacks extended into infancy or childhood. DESIGN This was a prospective, genetic clinic-based study, entailing clinical evaluation of black DS infants and children 3 months of age and older, and the administration of a questionnaire to the mothers of these patients. SETTING Genetics clinics at Kalafong and Ga-Rankuwa hospitals, Pretoria, and at Mankweng, Siloam, Groothoek, Nkhensani and Elim hospitals in the Northern Province. MAIN RESULTS Fifty-five DS infants and children were assessed. Their clinical features were comparable to those of children from other ethnic groups. Congenital heart disease (CHD) was recorded in a significantly higher percentage of infants under 12 months of age (51.9%) than children 13 months of age or older (25%). Only 9 (16.4%) of these DS patients were clinically diagnosed in the neonatal period, and a further 18 (32.7%) at between 1 and 6 months of age. More than half (28 or 50.9%) were 7 months of age or older when initially clinically diagnosed. Maternal self-initiated awareness of a problem with their infant or child preceded clinical diagnosis in 32 (58.2%) patients. CONCLUSIONS The difficulties experienced by medical and nursing staff in diagnosing DS in black neonates extends into infancy and childhood, despite the fact that the clinical features of black DS infants and children do not differ from those seen in DS patients in other ethnic groups. The prevalences of CHD in black DS infants and children suggest that CHD is a significant cause of mortality in black DS patients.