Dietary phosphate has profound effects on growth and renal handling of the compound. Based on changes in growth rate and food intake, following alterations in phosphate load, we previously suggested that these effects are mediated by intestinal signals (Landsman et al, Br. J. Nutr. 2001, 86:217-223). The aim of this study was to further evaluate the role of dietary phosphate on food-intake/appetite and specific organ growth, and to test for the presence of a serum factor that may affect renal phosphate handling in phosphate re-supplied rats. The experimental design was based on a comparison between groups of rats receiving identical low phosphate diets but drinking water containing either phosphate or chloride. We show that 1. Changes in food intake following alterations in phosphate load occurred in parallel with variations in digestive system distention, suggesting that dietary phosphate has also a direct effect on appetite. 2. Dietary phosphate-dependent growth has a specific effect on the growth of liver and epididymal fat, and 3. Serum of rats supplied with phosphate contains a factor that inhibits sodium-dependent phosphate transport in a model of renal proximal tubule cells. Collectively, these observations are in accord with the hypothesis that factor(s) emanating from the digestive system in response to dietary phosphate load, may be involved in growth, appetite and renal handling of phosphate.