Guinea-pig isolated vas deferens, in which the stores of noradrenaline (NA) had been labelled by preincubation with [3H]NA, was used to study the effects of substitution of chloride with other anions, on transmitter secretion evoked by electrical stimulation of postganglionic sympathetic nerves. Chloride was omitted from the Tyrode's solution and substituted with acetate, nitrate, methylsulphate, sulphate or HEPES. All substituents increased both the spontaneous and the stimulus-evoked fractional secretion of [3H]NA under control conditions. The effect was essentially the same at all frequencies of stimulation (1-8 Hz). In the presence of the alpha-adrenoceptor blocker phentolamine, which enhanced the secretion of [3H]NA in all media, the secretion was not further enhanced by chloride substitution. Chloride substitution reduced the depressing effect of exogenous NA on the secretory response. In conclusion, chloride ions may be required for full expression of alpha-adrenoceptor-mediated inhibition of [3H]NA secretion, but do not markedly influence facilitation by increased frequency of stimulation.