Our previous research showed enhanced immune responses, including mitogen-induced blastogenesis of peripheral blood mononuclear cells from feedlot calves and periparturient dairy cows supplemented with dietary chromium (Cr). The objective of the present study were to test whether blood sera from Cr-supplemented periparturient cows contained immunomodulatory activity for mitogen-stimulated peripheral blood mononuclear cells and, if so, to determine if this activity was explicable by differences in blood profiles of some glucose-regulating hormones (insulin, cortisol, growth hormone, insulin-like growth factor I, and tumor necrosis factor-alpha) between Cr-supplemented and unsupplemented (control) animals. Blood sera from ten unsupplemented cows and nine Cr-supplemented cows (0.5 ppm day-1) were collected weekly from 2 weeks before to 6 weeks after parturition, and were used to supplement (1, 10, and 20% vol/vol) culture medium supporting concanavalin A (Con A) stimulated mononuclear cells enriched from blood of four nulliparous donor cows. Hormone concentrations were determined using radioimmunoassays. Con A-induced blastogenesis was enhanced when 1, 10, and 20% sera from Cr-supplemented cows was added to the mononuclear cell cultures, and this was particularly evident around parturition. Conversely, peripartum sera from unsupplemented cows depressed Con A-induced blastogenesis. Except for a marginal rise in blood cortisol 2-4 weeks after parturition, no significant effects of Cr supplementation on other hormones (insulin, growth hormone, insulin-like growth factor I, tumor necrosis factor-alpha) were observed. These observations suggest that factors in peripheral blood serum from Cr-supplemented cows, other than absolute concentrations of the glucose-regulating hormones studied, modulate Con A-induced blastogenesis of mononuclear leukocytes.