OBJECTIVE: To evaluate the nature and magnitude of the effect of congenitally or perinatally acquired human immunodeficiency virus (HIV) infection on somatic growth from birth through 18 months of age. STUDY DESIGN: Anthropometry was performed serially in 282 term infants born to HIV-infected women in a multicenter prospective natural history cohort study. Repeated measures analysis was used to compare z-score anthropometric indexes of weight-for-age, length-for-age, weight-for-length, and head circumference-for-age between infected and uninfected infants, with adjustment for covariates including infant gender; maternal education; prenatal alcohol, tobacco, and/or illicit drug exposure; and mean prenatal CD4+ T-lymphocyte count. A separate repeated measures model was used to assess the effect of infant zidovudine treatment on growth. RESULTS: Infants infected with HIV were an estimated average 0.28 kg lighter and 1.64 cm shorter than uninfected infants at birth, were 0.71 kg lighter and 2.25 cm shorter by 18 months of age, and had a sustained estimated average decrement of 0.70 to 0.75 cm in head circumference. Patterns of growth were similar in male and female infants. Infected infants had a progressive decrement in body mass index from birth through 6 months of age. Infection with HIV was associated with significant decrements across all standardized growth outcome measures after adjustment for covariates. Mean z scores were lower for weight by 0.612 (p < 0.001), for length by 0.735 (p < 0.001), for weight-for-length by 0.255 (p = 0.02), and for head circumference by 0.563 (p < 0.001) SD units compared with uninfected infants. Zidovudine treatment was not associated with improved growth. CONCLUSION: The effect of congenitally or perinatally acquired HIV infection on infant growth is one of early and progressive decrements in attained linear growth and growth in mass, early and sustained decrements in head growth, and marked early decrements in body mass index.