The nude (athymic) mouse is currently used to study the effect of gastrin on cancer xenografts. We sought to develop a hypogastrinemic nude mouse model for use in evaluating the effect of hypogastrinemia on such xenografts. Thirty-six non-tumor-bearing nude mice were studied. Eighteen received a nutritionally complete liquid diet; eighteen received standard chow. Six mice from each group were weighed and killed (nonfasting) on days 2, 8, and 15. Mean serum gastrin levels ( f SEM) for the control group were 118.7 f 7.5, 118.7 f 8.7, and 118.0 + 7.5 pg/ml on days 2, 8, and 15, respectively. Serum gastrin levels for the liquid diet group significantly decreased to 87.0 f 7.6, 88.0 + 9.7, and 66.7 + 9.6 pg/ml on the same days. Animals in both groups gained weight normally; there were no significant weight differences between the two groups at any point. No histological abnormalities were seen in stomach, small intestine, colon, cecum, liver, pancreas, spleen or kidney. However, the liquid diet group showed atrophic changes in colon: significant reductions in colon weight and RNA content on days 8 and 15, and significant reduction in colon protein content on day 8. This model of hypogastrinemia is reliable and inexpensive. The nonsurgical nature of the preparation allows excellent survival in this immunodeficient animal.