Insulin-like growth factor-1 (IGF-1) is a natural protectant of cardiac myocytes that has been shown to improve cardiac function. The role of IGF-1 in attenuating apoptosis induced by osmotic stress (sorbitol, SOR) or by other known apoptotic stimuli (doxorubicin, angiotensin II, and serum withdrawal) was determined in cultured cardiac myocytes. After 6 h of exposure to SOR, apoptosis was initiated, concomitant with a decrease in cell survival and increases in poly[ADP-ribose] polymerase (PARP) degradation and DNA fragmentation. These effects were maximal after 24 h. IGF-1 partially attenuated apoptosis induced by sorbitol but not that induced by angiotensin II, doxorubicin, or serum withdrawal. In cells preincubated with IGF-1 before the addition of SOR, we detected an increase in the number of viable cells, a decrease in the generation of DNA fragments on agarose gel electrophoresis and in the percentage of positive TUNEL cells, and a reduction on PARP levels. These results suggest that IGF-1 prevents apoptosis induced by osmotic stress in cardiac myocytes but not apoptosis induced by doxorubicin and angiotensin II.