The roles of zinc in immune responses continue to be defined and its impact on a broadening list of immune functions reported. Fundamental to the operation of zinc-dependent processes may be shifts in tissue zinc. Since the spleen is a site of activation, proliferation, and differentiation of lymphocytes, we examined changes in copper and zinc levels in spleens of antigen-stimulated A/J mice. Antigen stimulation with human immunoglobulin G and heat killed Staphylococcus aureus was compared with the actions of a nonantigenic inflammatory agent CaCl2. Between-group variations in copper and zinc with antigen treatment were compared in heart, liver, and spleen tissues. The zinc contents of spleens from antigen-treated mice were elevated, as were liver levels of the essential trace element. There were no significant increases in copper levels associated with antigen treatment. CaCl2-treated animal spleens demonstrated decreases in spleen copper and zinc content that were related to weight changes in the spleens, but not to specific treatment effects. Changes were suggestive of Interleukin-1 (IL-1) actions, which led to direct studies of IL-1 actions on splenic zinc. Partially purified IL-1 was injected into the tail vein and heart of A/J mice; liver and spleen zinc levels were determined 16 and 40 hours after injection. Significant increases in liver and splenic zinc concentrations were measured at both time intervals after IL-1 treatment. Antigen stimulation and, more directly IL-1, were related to stimulated increases in splenic zinc.(ABSTRACT TRUNCATED AT 250 WORDS)