Primary normal alcohols (1-n-alkanols) exert two effects on the nicotinic acetylcholine receptor when added simultaneously with agonist. First, propanol through decanol inhibit the open channel. Second, methanol through butanol, but not higher homologs, increase the apparent affinity of the agonist for inducing cation flux. To test the hypothesis that the length or volume of the alcohols might account for the fact that some members of the 1-n-alkanol homologous series lack activity, we have studied in parallel 11 members of another homologous series, i.e., the cycloalkanemethanols, c(CnH(2n-1)CH2OH. With steadily increasing potency, agents from cyclopropanemethanol to cyclodecanemethanol completely inhibited carbachol-stimulated 86Rb+ efflux from nicotinic acetylcholine receptor-rich postsynaptic vesicles from the electroplaques of Torpedo nobiliana, but even 90% saturated solutions of cycloundecanemethanol inhibited only part of the flux and neither cyclododecanemethanol nor cyclotetradecanemethanol caused any inhibition. Comparison of these results with those previously obtained for 1-n-alkanols indicates that as both series are ascended the cut-off in the inhibitory action on the channel occurs when the volume of the compounds exceeds approximately 340 A3. The apparent affinity for carbachol-induced flux was enhanced only by cyclopropanemethanol through cyclooctanemethanol, consistent with the hypothesis that a critical length of approximately 6.3 A cannot be exceeded. Thus, the sites mediating the two effects have different steric requirements and may be physically distinct.