In frog''s sartorius and isolated nerve-muscle fibre preps. of the M. adductor longus, reduction of ionized Ca in the surrounding fluid affects the endplate region prior to the nerve endings and muscle fibres. Spontaneous activity resulting after immersion into citrate or Ca-free saline solns. originates primarily at the endplates. Reduction of Ca to 1/3-1/5 of normal first increases the excitability of the endplates as judged by repetitive response to a single nerve impulse. Also the sensitivity of the endplates to applied acetylcholine is 100-1000 times increased. Subsequently neuro-muscular block results while the nerve endings still conduct impulses and the muscle action potential set up by direct electric stimulation is not appreciably altered. It is suggested that the block is due either to diminished production of the "transmitter," or to diminish electric excitability of the endplate region. The part of the sartorius immersed into Ca-free or Ca-deficient saline becomes negative relative to the rest of the muscle. Excess of ionized Ca gradually blocks nerve-muscle transmission presumably by lowering the electric excitability of the muscle fibre adjacent to the endplate.