Somatostatin (SS) and its analogue inhibit the growth of some human tumors in vivo. Surprisingly, we found that SS-14 and its analogue (SMS 201-995) exhibited unexpected proliferative effects on two lines of cells, A431 and KB human epidermoid carcinoma cells, in vitro. The level of intracellular cyclic AMP, an important second messenger that controls the growth of A431 cells, was unaffected in A431 cells by either SS-14 or SMS 201-995. In contrast, SS-14 (20 nM) and SMS 201-995 (10 nM) reduced the level of intracellular inositol 1,4,5-trisphosphate rapidly but transiently.