Sequential development of Leishmania promastigotes from a noninfective to an infective stage has been observed for parasites growing both within culture and the sandfly vector. The generation of infective stage promastigotes is growth cycle related and restricted to non-dividing organisms. Thus, parasites taken from the logarithmic phase of growth in culture and the sandfly midgut are relatively avirulent for a susceptible vertebrate host (BALB/c mice), whereas those taken from stationary cultures or later midgut infections are highly virulent. The increase in virulence is related to the parasite's ability to resist the normal microbicidal activities of host macrophages, and not in their ability to gain entrance into these cells. A comparison of the susceptibility of log and stationary promastigotes to oxygen-dependent antimicrobial mechanisms revealed that the latter were 2-3 times more resistant to the lethal effects of the oxygen intermediate, hydrogen peroxide. This could explain the ability of infective stage promastigotes to survive the respiratory burst triggered by the rapid uptake of these organisms. Infective and non-infective stage promastigotes can be separated on the basis of their differential binding to the lectin, peanut agglutinin. Comparison of these relatively homogeneous stage specific populations will permit further identification of those specific antigenic, biochemical, and physiological changes which accompany transition of these parasites from invertebrate to vertebrate environments and which determine the successful parasitism of Leishmania within the vertebrate host.