The design of effective prophylactic measures to prevent the vertical transmission of HIV-1 and of therapies to alter the natural progression of pediatric HIV disease requires a thorough understanding of basic pathogenetic principles. Maternal viral load, the biological behavior of HIV, such as replicative capacity in different types of cells, monocyte/macrophage tropism, and the capacity of the infant's cells to support infection have all been assessed for their contribution to the risk of mother-to-child transmission. Similarly, the effects of viral load and phenotype (e.g. replicative capacity, cell tropism, syncytium-inducing capacity and the use of chemokine co-receptors) have all been investigated as parameters associated with variations in the expression of clinical disease in children. Some of the extant data are conflicting, but general principles regarding pathogenesis are beginning to emerge.