The role of oyster shell as calcium supplement in the utilization of gossypol-containing cottonseed cake (CSC) was assessed using Hypeco broiler chickens. The results showed that of the organ measured, only the relative weight of the spleen was significantly (P less than 0.05) decreased by oyster shell supplementation in the CSC diets. Spleen weight correlated negatively (r = -0.45) with dietary calcium. Alkaline phosphatase activity in the liver was significantly (P less than 0.05) increased due to the levels of oyster shell supplemented while the activities of serum and liver alanine aminotransferase and aspartate aminotransferase were not significantly influenced. The results also showed that although oyster shell supplementation generally increased alkaline phosphatase activity, bone mineralization was relatively uninfluenced as judged by the low coefficients of variation (CV) of 3.14-3.51% and 3.39-4.82% for calcium and phosphorus content in the femur and tibia respectively.