Three hundred and forty-five dogs with mammary tumors were initially evaluated for study. One hundred and forty-four dogs with untreated malignant mammary tumors (136 adenocarcinomas, 5 malignant mixed, 3 sarcomas) were selected for study. All dogs were clinically staged and stratified on the basis of tumor volume and body weight. Dogs were randomized to either a radical mastectomy or simple mastectomy group, and then further randomized to a levamisole or placebo group. There was no significant difference in either survival time or cancer-free survival time between the surgery groups or between the levamisole and placebo groups. The most significant prognostic factor was tumor volume; dogs with tumors less than 41 cc had significantly enhanced survival time (p = 0.0007) and cancer-free survival time (p = 0.0005).