The effects of culture supernatants from different dinoflagellate (Alexandrium and Prorocentrum) clones on the activities of caspases involved in apoptotic pathway were determined. Exposure of rat pheochromocytoma PC12 cells and rat primary neuronal cells to toxic supernatants from A. lusitanicum ME-091, A. lusitanicum K2, A. tamarense 1M, and A. tamarense ccmp 115 for 1 to 3 days resulted in a time-dependend increase (of up to 188%) in the specific activities of caspases 1 (ICE), 3 (CPP32) and 6 (Mch2). The extent and the time point of the maximal increases in caspase activities varied between the different dinoflagellate clones. A significant increase in the specific activities of caspases 1, 3 and 6 was also observed after treatment of neurons with the supernatants of P. lima ME-130 clones K1 and K2. The maximal increases in caspase activities in PC12 cells (CPP32, 364%; and Mch2, 166%) and in neurons (CPP32, 162%) were observed 24 h after treatment with the P. lima ME-130 K1 supernatant. Among the isolated dinoflagellate toxins tested, saxitoxin caused a strong increase (up to 205%) in all three caspase activities in neuronal cells but not in PC12 cells. Tetrodotoxin had, if at all, only in a small effect on caspase activities in these cells. The protein phosphatase inhibitor okadaic acid caused a time-dependent increase in caspase activities in PC12 cells. A much higher effect was observed in neuronal cells. These results indicate that induction of apoptosis in PC12 cells and primary neuronal cells by toxic dinoflagellate supernatants and isolated dinoflagellate toxins may be mediated by an activation of intracellular caspase activities. Supported by the German BMBF, TEPS Project