The ability of C3H/He mammary carcinoma cells to grow in the lungs after i.v. injection was repeatedly tested with cells from tumors which were kept in serial s.c. passage in syngeneic female mice. The s.c. growth rate and the s.c. transplantation immunogenicity were also determined for each transplant generation. The ability of a tumor to grow in the lungs, which appeared in most tumors only after repeated s.c. passages, coincided mainly with increased growth rate and not with the loss of immunogenicity and/or gain of endogenous growth-stimulating factors. In each combination of cross-reactivity tested, transplantation immunogenicity was tumor specific, and growth stimulation was not tumor specific. Three of ten tumors were retested in serial passages started again from pieces of the primary tumors stored in liquid N2, and the identical changes recurred in the same, or in nearly the same, transplant generations. This indicates that certain variable neoplastic characteristics may be inherent and will appear not haphazardly, but according to a genetically predetermined schedule.