The effect of ionophoretically applied pentobarbital (PB) upon neurones in the nucleus reticularis gigantocellularis of the rat was studied. PB applied through a micropipette depressed the spontaneous activity of 81% of the neurones tested; the remaining neurones did not change their firing rates. Regardless of current intensities used for PB ejection (5-60 nA) there was no increase in the firing rate during PB administration. The depression was dependent upon both the control firing rate and the PB dose; a total depression of activity was observed at currents between 40 and 60 nA. EC50 (15.5 nA, about 5 X 10(-5) mol.l-1--the drug concentration was approximated theoretically) was assessed from the dose-response curve. Repeated application resulted in a shift of EC50 towards higher current values (desensitization). The Hill coefficient was calculated in conformity with the classical theory. From its value (1.4), it may be assumed that the occupation of only one subunit of the binding site is enough to give a response. Possible mechanisms of action of PB upon neurones are discussed.