The effects of feeding whole cottonseed (WCS) and bovine somatotropin (bST) administration on hematological responses and plasma alpha-tocopherol concentrations of lactating dairy cattle were examined. After parturition, multi and primiparous Holstein cows (n = 159) were assigned randomly to a 2 x 2 factorial arrangement of treatments consisting of (0 or 15% WCS and 0 or 208 mg of bST injected every 2 wk starting within 7 d after calving. Blood samples were collected from a subset group of 64 cows at 14, 28, 42, and 56 d postpartum. Blood was collected from all cows (n = 159) at 75, 96 and 120 d postpartum. Blood samples were analyzed for alpha-tocopherol and total and (+)- and (-)-gossypol in plasma. Erythrocyte osmotic fragility, hemoglobin and hematocrit also were determined in blood. The mean concentrations of alpha-Tocopherol, total, and (+)- and (-)-gossypol were higher in cows fed WCS regardless of bST administration and plateaued by d 75 postpartum. Hematocrit and hemoglobin concentrations were not affected by treatments. Erythrocyte osmotic fragility was higher in cows fed WCS, but the increase was attenuated when bST was injected (diet x bST interaction). No clinical signs of gossypol toxicity were observed in the cows consuming the WCS.