Although Dale and his colleagues first identified acetylcholine in 1914 as a possible neurotransmitter, Loewi showed its importance in the nervous system. The two men shared the 1936 Nobel Prize for Medicine.

During the 1940s Dale was embroiled in the scientific debate over the nature of signaling at the synapse. Dale and others believed that signaling at the synapse was chemical, while John Carew Eccles and others believed that the synapse was electrical. It was later found that most synaptic signalling is chemical, but there are some synapses that are electrical.