Approximately one-third of low-income women and children studied in Guatemala are reported to have deficient (<148 pmol/L) or marginal (148-220 pmol/L) plasma vitamin B-12 concentrations. Because vitamin B-12 deficiency can adversely affect infant development and cognitive function, the present study examined predictors of deficient plasma vitamin B-12 concentrations at the age of 12 mo. Analyses were performed on baseline data from a randomized clinical trial in 304 Guatemalan infants, 80% of whom were partially breast-fed, and their mothers. Exclusion criteria for infants included twins, severe stunting or moderate wasting, reported major health problems, severe developmental delay, hemoglobin <95 g/L, maternal age <17 y, and maternal pregnancy >3 mo. Data collected included socio-economic status, infant anthropometry, vitamin B-12 intake from complementary foods, and breast-feeding frequency reported by mothers. A complete blood count and plasma vitamin B-12, folate, ferritin, and C-reactive protein were measured. Deficient or marginal plasma vitamin B-12 concentrations were found in 49% of infants and 68% of mothers. The mean intake of maternal vitamin B-12 was 3.1 microg/d, and infants consumed 2.2 microg/d from complementary foods. In linear regression analysis, infant plasma B-12 concentration was strongly and positively associated with maternal plasma vitamin B-12 and B-12 intake from complementary foods (predominantly powdered cow's milk), and inversely associated with frequency of breast-feeding and larger household size (P < 0.0001). Vitamin B-12 supplementation of lactating women, food fortification, and education to improve infant's vitamin B-12 status are potential interventions that can improve the vitamin B-12 status of mothers and infants in this population.