several enzymes that contribute to immune system responses require zinc and copper as trace elements for their activity. we examined zinc and copper levels in two susceptible balb/c mouse lines and resistant c57bl/6 mice infected with leishmania major mrho/ir/75/er, a prevalent strain that causes cutaneous leishmaniasis in iran. serum zn and cu were determined by flame atomic absorption spectrophotometry. higher cu levels were found in infected c57bl/6 mice and higher zn levels were found in infected balb/c mice. also, cu/zn ratios were increased in both the balb/c and the c57bl/6 mice. we conclude that concentrations of essential trace elements vary during cutaneous leishmaniasis infection and that this variation is associated with susceptibility/resistance to leishmania major in balb/c and c57bl/6 mice. we detected zn deficiency in the plasma of infected balb/c mice; possibly, therapeutic administration of zn would be useful for treating this form of leishmaniasis. increases in cu level might increase resistance to leishmaniasis. based on our findings, the cu/zn ratio could be a useful marker for the pathophysiology of leishmaniasis.