Abstract: The circumsporozoite (CS) protein of Plasmodium falciparum has been analyzed to develop a new anti-sporozoite malarial vaccine. Localization of sites for T-cell recognition on this molecule is critical for vaccine design. By using an algorithm designed to predict T-cell sites and a large panel of H-2 congenic mice, a major nonrepetitive T-cell was located. When a synthetic peptide corresponding to this site was covalently linked to the major B-cell site on the molecule, an immunogen capable of eliciting a high titer antibody response was formed. This peptide sequence is capable of priming helper T-cells for a secondary response to the intact CS protein. This site represents the first helper T-cell site described for the CS molecule outside of the repetitive region, and is a major immunodominant T-site on the molecule. The approach described herein is useful in the rational design and construction of more efficacious vaccines.