Cell mediated immunity is very important for host defence against intracellular pathogens and many studies have shown the role of the production of nitric oxide (NO) by interferon (IFN)-γ/lipopolysaccharide (LPS)-activated macrophages. As the progesterone level increases during pregnancy in mammals, and as previous studies have shown that progesterone inhibits inducible nitric oxide synthase (iNOS) expression and NO production, we aimed to investigate whether progesterone might modulate intracellular replication of Toxoplasma gondii in macrophages. Our results showed that progesterone does not influence T. gondii replication in non-activated RAW 264·7 cells, and although progesterone inhibits NO production induced by IFN-γ/LPS, we observed that it fails to restore the growth of T. gondii blocked by IFN-γ/LPS. After discussing the reasons for this apparent discrepancy, we concluded that progesterone has no direct effect on the macrophage response. The real effect of the sex steroids in T. gondii infection and their implication in clinical toxoplasmosis therefore need to be investigated further to involve wider mechanisms of the immune system.