Amastigotes and promastigotes of Leishmania donovani were used as antigens for immunization of rabbits which produced anti-amastigote IgG demonstrable by indirect immunofluorescent tests. Effects of these and normal rabbit heat-inactivated sera on phagocytosis of amastigotes by a mixture of human mononuclear and polymorphonuclear phagocytes were studied in vitro. Parasites and phagocytes at different ratios were mixed and incubated at 37°C for various time periods in the presence of these sera at different dilutions. In all cases, phagocytosis of amastigotes was higher in neutrophils than in monocytes, and in most cases increased with time in both. The numbers of intracellular amastigotes were, however, consistently lower in cultures with anti-amastigote antiserum (anti-A) than in those with anti-promastigote antiserum (anti-P) or normal rabbit serum. The differential effect of anti-A and anti-P implies differences in antigenic determinants between these two leishmanial forms. A similar, but less pronounced, effect of anti-A was also observed by using opsonized parasites. Experiments were also carried out with phagocytes from subjects of congenital chronic granulomatous disease (CGD) whose polymorphonuclear phagocytes were shown earlier to have only limited leishmanicidal activity. Results of kinetic study and those with CGD cells suggest that inhibition of phagocytosis rather than enhanced leishmanicidal activity accounts for the anti-A-mediated decrease of intracellular amastigotes in human phagocytes. Blockade of phagocyte Fc receptors by soluble antigen-antibody immune complexes released during incubation is proposed as a possible mechanism of this inhibition for future investigation.