Scientific and public concerns on perfluorinated compounds (PFCs) are increasingly growing because of their environmental persistency, bioaccumulation, and extensive distribution throughout the world. Little is known about the effects of PFCs on neural function and the underlying mechanisms. Recent evidence suggests that the toxicological effects of PFCs are closely correlated with their carbon chain lengths. In this present work, the actions of PFCs with varying chain length on cultured rat hippocampal neurons and possible action patterns were examined. Increases in the frequencies of spontaneous miniature postsynaptic current (mPSC) were commonly found in cultured neurons when perfused with PFCs. The increase of mPSC frequency was in proportion to the carbon chain length, and the potency of perfluorinated carboxylates was less pronounced than that of perfluorinated sulfonates. A comparable but less perceptible trend was also found for the amplitudes of voltage-dependent calcium current (I_Ca). No regular change in pattern was observed for the effects of PFCs on activation and inactivation kinetics of I_Ca. Furthermore, prolonged treatment of PFCs inhibited the neurite growth of neuronsto various degrees. Comparisons between nonfluorinated and perfluorinated analogues demonstrated thatthefluorination in alkyl chain exerts stronger actions on neurons as compared to the surfactant activity. This study shows that PFCs exhibit adverse effects on cultured neurons to various extents, which is dependent on the carbon chain length and functional group attached to the fully fluorinated alkyl chain.