The metastatic behavior of seven human tumor cell lines grown in young (3- to 4-week-old) nude mice was studied. Two cell lines were derived from malignant melanomas, one from a colon carcinoma, two from prostate adenocarcinomas, and two from renal adenocarcinomas. Many of the cell lines produced metastases after i.v. injection (experimental metastasis) and after s.c. transplantation (spontaneous metastasis) into young nude mice. The incidence of metastasis seemed dependent primarily on the biological characteristics of the individual tumor cell line. However, the incidence of metastasis of some tumor cell lines could be increased by isolation and establishment of variant sublines from secondary tumor deposits, by prolonged systemic administration of 17β-estradiol to suppress natural killer cell activity, and/or by use of an advantageous site of tumor implantation. Intrasplenic injection of tumor cells allowed the most dramatic overall expression of metastatic capacity in these cell lines, resulting in frequent and large metastases to liver, lungs, and the mesenteric, omental, and mediastinal lymph nodes.