Earlier, we reported that prophylactic treatment with human interferon gamma (rHuIFN-gamma) protected monkeys against Plasmodium cynomolgi B malaria infection. We have tested the efficacy of rHuIFN-gamma on relapsing stage of experimental P. cynomolgi B malaria infection in rhesus monkeys. No effect of rHuIFN-gamma was seen against experimental relapsing stage compared with controls; however, it appears that chloroquine (CHL) may have interfered with the antimalarial effect of IFN, since treatment with CHL inhibits the antiviral activity of mouse alpha/beta IFN and polyinosinic-polycytidylic acid (poly I:C) against Semliki forest virus (SFV) in mice. These results may have clinical implications especially with the use of IFN against virus infection, cancer and in parasitic infections in malaria endemic areas where CHL is one of the most widely used antimalarial drugs. Our result also shows that CHL treatment enhances the virus replication in mice and suggest a possible connection between AIDS and malaria infection, since the spread of AIDS has been rapid in parts of tropical Africa that have a high incidence of malaria, and chloroquine has been frequently used in the chemotherapy of malaria.