Intracellular recordings were made from neurons in dissociated cell culture of neocortex during application of norepinephrine (NE) or other adrenergic agonists. In the population of neurons generally studied, greater than 18 micron in diameter, adrenergic agonists from 1 nM to 50 microM produced no change in membrane potential or input resistance 120 cells). Adrenergic agonists increased synaptic activity impinging on the impaled cell in 25/120 neurons (21%). In neurons in cocultures of locus coeruleus and cerebral cortex, again the same synaptic response to perfusion with NE was noted in 13/93 neurons (14%). In addition, direct effects of NE were noted on 6/93 neurons recorded from in cocultures, all close to the explant. In these cells, NE hyperpolarized the membrane in association with a small decrease in input resistance (11%). These responsive cells may have originated within the explant. A paradigm was used for testing the possibility of a responsive element in the cultures distinct from the impaled soma. 'Hot spots' were found using concentrations of isoproterenol as low as 10 nM.