Most investigations on the effect of immunogenic challenge on trace-mineral metabolism use a single immunogen injection in fasted animals. Because these investigations are not representative of realistic situations in which animals are constantly exposed to immunogens and still consume feed, the following studies were done. In Expt. 1, chicks were injected ip with sheep red blood cells (SRBC), Sephadex, SRBC+Sephadex, or saline. Chicks were then fasted or fed equal amounts of feed (equal fed) for 16 h. Immunogen injection decreased serum Fe and Zn and increased serum Cu within each feeding program. Differences in Cu, and to a lesser extent Zn, concentrations between immunogen- and saline-injected chicks were more pronounced in fasted than in equal-fed chicks. In Expt. 2, equalfed chicks were injected ip every 48 h for 6 d with SRBC+Sephadex or saline. Two days after each injection, tissues were taken. An additional group of chicks was injected once and subsequently fasted 16 h, whereupon tissues were taken. Changes in plasma Fe, Zn, Cu, and ceruloplasmin; hepatic Fe, Zn, Cu, and metallothionein; pancreatic Fe and Zn; and splenic Fe in repetitively injected chicks were different from changes observed in chicks injected once. The results indicate that the trace-mineral response to immunogenic challenge is dependent upon the number of immunogen injections and the nutritional state of the animal.