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1. Vascular responses and noradrenaline overflows have been studied in the isolated blood-perfused cat spleen in response to electrical stimulation of the splenic nerve with trains of 200 supramaximal pulses at a frequency of 10 Hz given at 10 min intervals.

2. In the absence of blocking agents the spleen gave well-defined responses and a mean maximum overflow of 436 ± 96 pg noradrenaline per stimulus (n = 4) at the third train of stimuli.

3. Cocaine (2 x 10^-5 M) increased the response nearly threefold and raised the overflow to 840 ± 131 pg/stim (n = 4). At later stimulations the responses remained stable, but the overflows rose progressively to 1076 ± 51 pg/stim after five trains of stimuli.

4. Normetanephrine (10^-4 M) had no significant effect on response, but elevated the overflow to a mean maximum of 868 ± 169 pg/stim (n = 4).

5. Cocaine (2 x 10^-5 M) and normetanephrine (10^-4 M) given together increased the response by a factor of 6·5 and raised the overflow to 1258 ± 247 pg/stim (n = 4).

6. Hydergine (approx. 10^-5 M) almost completely abolished the response and raised the overflow to 859 ± 173 pg/stim (n = 4).

7. Cocaine (2 x 10^-5 M), normetanephrine (10^-4 M) and hydergine (approx. 10^-5 M) given in combination abolished the response and raised the overflow to 4089 ± 1148 pg/stim (n = 4).

8. Phenoxybenzamine (10^-4 M) abolished the response and elevated the overflow to 4215 ± 738 pg/stim (n = 4).

9. These results are interpreted in terms of selective and combined block of `uptake I', `uptake II' and -adrenergic receptors. Facilitation of transmitter release by -blocking drugs, and the possible existence of an uptake process associated with the -receptors are discussed.

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