The growth and metastatic behavior of human tumor cell lines were studied in nude, beige/nude/xid (bg/nu/xid) and severe combined immunodeficient (SCID) mice. One melanoma, two colon carcinomas and one renal carcinoma grew subcutaneously in the three strains of mice with no significant differences in tumor take and growth rate. One ovarian carcinoma formed a subcutaneously growing tumor only in SCID mice. Spontaneous metastases were observed only in mice with advanced subcutaneous tumors or at histological examination, but more frequently in bg/nu/xid and SCID mice than in nude mice. A375M melanoma formed more lung colonies in nude and bg/nu/xid mice than in SCID mice. HT-29LM colon carcinoma injected intravenously or intrasplenically formed more lung and liver colonies and lymph node metastases in bg/nu/xid mice than in nude and SCID mice. The treatment of SCID mice with anti-asGM1 serum depleted NK activity and enhanced the number of lung colonies by A375M melanoma and HT-29LM colon carcinoma. Bg/nu/xid or SCID mice may therefore offer some advantages for studying the malignant behavior of human solid tumors and differences may depend on the experimental conditions and on the tumor type.