In a series of transplant experiments, we investigated interactions between normal, ductal phase, and tumorous phase mammary tissues in GR/A mice, with particular respect to growth regulation. Transplants from hormone-dependent mammary tumors (HDT) transplanted into mammary fat pads already containing normal mammary ducts usually could not be located subsequently or, at best, displayed minimal growth. Growth regulation was also normal when two HDT transplants, placed in a single gland-free fat pad in nonpregnant hosts, produced ductal outgrowths displaying mutual avoidance behavior in which ducts did not touch and were normally spaced. A normal and HDT transplant in a single gland-free fat pad also showed identical, normal regulatory behavior. In contrast, HDT transplants in pregnant hosts or in hosts receiving exogenous hormone therapy displayed altered growth patterns in which neighboring tumors touched and eventually fused. When surrounded by normal tissues, the HDT continued to proliferate and often appeared to overgrow and engulf normal elements. We concluded that HDT tissues grown in nonpregnant hosts fully responded to those short-range regulatory influences characteristic of normal morphogenesis. When exposed to hormones of pregnancy, however, these interactions changed, and HDT tissues exhibited many characteristics of ductal carcinomas.