In several prospective studies during the past 5 years, we evaluated 400 patients with nonseminomatous and 60 with seminomatous testicular tumors with the use of serum and cellular AFP and HCG at the NCI. Ninety percent of the patients with nonseminomatous testicular tumors had elevated levels of either HCG and/or AFP that have been useful in detection, staging, prognosis, and monitoring the efficacy of the therapeutic modalities. Although 5% of the patients with pure seminoma had an elevated level of serum HCG, one must search for elements of nonseminomatous testicular tumor in these patients by serial section of the seminoma specimen. Elevated serum AFP in patients with designations of seminoma indicates the presence of an element of embryonal carcinoma and/or teratoma. We have localized these markers in various tumor cells by using the technique of indirect immunoperoxidase. The HCG is localized in syncytiotrophoblastic component of choriocarcinoma and syncytiotrophoblastic giant cells occasionally found in association with embryonal carcinoma, teratoma, and seminoma. The AFP is localized in embryonal and endodermal sinus tumor.