Female B6C3F1 mice treated with 25 mg/kg pyran intravenously (i.v.) on days -4 and -3 were more susceptible to nonlethal Plasmodium yoelii 17XNL or lethal Plasmodium berghei ATCC-30090 than untreated mice or mice treated intraperitoneally (i.p.). Female B6C3F1 mice treated with pyran i.p. displayed enhanced resistance to Listeria monocytogenes as compared to untreated mice or mice given pyran i.v. Peritoneal exudate cells (PEC) primed by pyran i.p. possessed enhanced ability to kill Listeria but impaired ability to destroy Plasmodium. Phagocytosis of Covaspheres by PEC was greater for mice given pyran i.p. than those given pyran i.v. Chemiluminescence evoked by zymosan was less for PEC from mice given pyran i.v. than for those from untreated mice or those given pyran i.p. Chemiluminescence was greater for adherent splenocytes from mice treated with pyran i.p. than for those from untreated mice or those from mice treated i.v. Pyran administered i.v. is less effective in modulating the host immune response than pyran administered i.p. Immunomodulatory agents such as pyran have adverse as well as beneficial effects depending upon the route of administration.