OBJECTIVE: To estimate the role of human milk n-6 and n-3 polyunsaturated fatty acids (PUFA) in term infant growth in two African urban populations. DESIGN: Observational study. Weight gains at 5 months of age and dietary habits were compared between Congolese infants (n=102) and Burkinabè infants (n=101). Socio-economic status and anthropometry of the mothers were also recorded. SETTING: One suburban district in Brazzaville (capital of The Congo) and one in Ouagadougou (capital of Burkina Faso). SUBJECTS: Two random samples of nursing mothers and their 5-month-old infants. RESULTS: All infants were born at term and there was no difference in birth weights. At 5 months of age, infants in Ouagadougou were thinner but not shorter than their counterparts in Brazzaville (average weight gain (standard deviation): 614 (168) g month-1 vs. 720 (176) g month-1; P= 0.0001). Drastic differences were found in infant diets with regard to extra fluid intake and n-6 and n-3 PUFA concentrations in breast milk. In Ouagadougou, all infants were given fluids other than milk from birth. Breast milk had highly unbalanced 18:2n-6/18:3n-3 and n-6/n-3 long-chain PUFA ratios (53:1 and 5:1, respectively). In Brazzaville, half of the infants received fluids other than milk, and breast milk showed balanced 18:2n-6/18:3n-3 and n-6/n-3 long-chain PUFA ratios (12:1 and 1:1, respectively). A non-linear relationship between 18:2n-6/18:3n-3 ratio and growth was established in Brazzaville (P= 0.0027). The 18:2n-6/18:3n-3 ratio adjusted with covariates had an even more significant effect on weight gain (P= 0.0011). Applying the same model in Ouagadougou did not show such a relation. CONCLUSION:: Data strongly suggest that a balanced ratio of 18:2n-6/18:3n-3 (between 5:1 and 15:1) in breast milk leads to higher weight gain of infants during the first 5 months of life.