Objective - To determine the effect of exogenous growth hormone or somatostatin on chemotherapeutic efficacy in athymic (nude) rats with osteosarcoma. Animals - 66 female athymic rats. Procedure - Osteosarcoma was induced at an intratibial site. Rats were randomly allotted to 6 treatment groups. Rats were treated with saline (0.9% NaCl) solution alone, platinum, diammine [1,1-cyclobutane dicaboxylato (2-)-0,0']-(SP-4-2) (CBDCA; ie, carboplatin) plus saline solution, somatostatin alone, somatostatin plus CBDCA, growth hormone alone, or growth hormone plus CBDCA. Variables measured included estimated WBC count and percentage of neutrophils, plasma concentration of insulin-like growth factor I (IGF-I), body weight, tumor volume, weight of primary tumor, survival time, and distant metastasis at time of death. Results - Tumors formed at the injection sites in all rats. Treatment with growth hormone increased, and treatment with somatostatin decreased, plasma IGF-I concentration. Treatment with growth hormone or somatostatin altered CBDCA efficacy, as determined by evaluation of mean and median survival times. Metastatic pulmonary disease developed in 63 of 64 rats. Conclusions and Clinical Relevance - The technique used here reliably induced local osteosarcomas and metastatic pulmonary disease. Treatment with growth hormone and CBDCA or somatostatin may improve chemotherapeutic efficacy without increasing toxic effects. Implications for Human Medicine - Results reported here may be useful in the study of osteosarcoma in humans.