The effects of the central administration (i.c.v.) of dibutyryl cyclic AMP (DBcAMP) on arterial blood pressure and heart rate were studied in the rat. The cyclic nucleotide produced a dose-dependent rise in blood pressure and an accompanying tachycardia. Maximal pressor effect of a single dose of DBcAMP (350 micrograms) was observed 25 min post injection and the duration of the response was 60 min. Chemical degeneration of central catecholaminergic neurons with 6-hydroxydopamine treatment abolished the pressor response to DBcAMP. Partial chemical degeneration of central serotonin pathways with 5,6-dihydroxytryptamine did not significantly alter the effect. The pressor activity of the cyclic nucleotide was attenuated by central administration of phentolamine. Spinal cord section at the C6-C7 level or peripheral chemical degeneration of catecholaminergic neurons combined with bilateral adrenalectomy abolished the pressor response to DBcAMP. It was concluded that the pressor response to i.c.v. administration of DBcAMP is mediated by central catecholaminergic pathways and is the result of an increase in efferent sympathetic outflow and release of catecholamines from the adrenal medulla.