IN a recent letter, Chothia and Pauling1 comment on our paper dealing with the determinants of specificity at cholinergic synapses2. They correctly point out that we do not define the conformation of acetylcholine which is responsible for its action at nicotinic sites. Moreover, they present a calculation to show that because the acetylcholine ester grouping is not planar in the conformation shown in the figures, it represents only a negligible proportion of the molecules in solution. From this they conclude that this model of acetylcholine is not relevant to the roles of the molecule as a neurotransmitter.