Cyclic inositol phosphohydrolase (cIPH) (EC 18.104.22.168) hydrolyzes the cyclic phosphodiester bond of cyclic inositol monophosphate to yield inositol 1-phosphate. Renal tissue in various species has been shown to contain the highest activity of this enzyme. Cyclic inositol monophosphate, the substrate for this enzyme, has been implicated in the regulation of cell density. Thus, we determined whether activity of this enzyme is modulated in renal tumor. Samples of hamster renal tumors induced by diethylstilbestrol (DES) demonstrated 87% less cIPH activity than control hamster kidney. After 8 days of DES treatment of hamsters, a 28% decrease in the cIPH activity in kidney was observed. Interestingly, comparison of the cIPH activity in normal human kidney cortex, medulla, and renal cell carcinoma gave the following values (mean ± SD), 10.6 ± 4.6 (9), 6.7 ± 4.6 (5), and 1.9 ± 2.3 (8), respectively. Our study demonstrates that cIPH activity is reduced in hamster and human renal tumors. © 1995 by Academic Press, Inc.