The evolution of cells of the monocyte-macropbage lineage (MML cells) in the spleen of Leishmania donovani (LD) infected BALB/c mice was studied. Spleen cells were fractionated on a discontinuous percoll gradient and adherent cells (AC) were purified from fractionated spleen cells by adherence steps that appeared at the interfaces of 25–35%, 35–40%, 40–45% and 45–50% percoll gradients. The AC were characterized as MML cells on the basis of positive staining for non-specific esterase. Adherent cells that appeared at the interfaces of 25–35% and 40–45% were defined as A and C, respectively, and both of them showed extreme variation in a progressive infection. It was observed that A supported parasite replication whereas C remained refractory when infected with LD in vitro. Furthermore, when A cells and C cells were used as antigen-presenting cells to stimulate mixed population of IFN-γ producing and IL-4 producing T-cells, it was observed that IL-4 and IFN-γ were the predominating cytokine in the T-cell supernatant, respectively. Both A and C were found to be increased hand-in-hand up to 5 months of infection and from then on A decreased and C increased in their numerical strength (A-C reciprocity). The evolution of A-C reciprocity coincided with the gradual reduction in the parasitaemia in the spleen suggesting that this may contribute to the acquisition of anti-leishmania immunity.