1. Using a grease-gap technique, we studied the action of histamine on the d.c. potential recorded between the internal carotid nerve and the main body of the isolated superior cervical ganglion of the rat. 2. A small, slow depolarization was evoked by 10-300 microM histamine. This response was not reduced by lowering the calcium concentration in the superfusing medium (from 2.5 to 0.1 mM), or by superfusing tetrodotoxin, N-methylatropine, or propranolol (all at 1 microM). 3. Mepyramine (10 nM) antagonized this depolarization, but cimetidine (10 microM), metiamide (30 microM), burimamide (10 microM) and impromidine (1 microM) did not. Two other agonists also evoked a mepyramine-sensitive slow depolarization. The rank order of potencies was histamine greater than N alpha-methyl-histamine greater than 2-methyl-histamine. 4. At concentrations greater than 1 mM, histamine also evoked a larger, faster depolarization. This response was undiminished by reducing the calcium concentration of the medium to 0.1 mM or by adding 1 microM tetrodotoxin. The rank order of potency for the agonists was N alpha-methyl-histamine greater than histamine approximately 2-methyl-histamine. The histamine-induced fast response was not antagonized by any of the above-mentioned antagonists. It was slightly reduced by (+)-tubocurarine (100 microM) and N-methylbicuculline (100 microM) but such effects were not consistent with the blockade of nicotinic or GABAA receptor-mediated responses. 5. It was concluded that histamine depolarized the isolated superior cervical ganglion of the rat by activating H1 receptors. Relatively high concentrations of histamine also evoked a fast depolarization of this preparation, but this did not appear to be mediated by H1, H2 or H3 receptors.