1 The effects of cocaine and lignocaine on the contractile responses to field stimulation and to exogenously applied agents, in the absence of other stimuli, have been investigated in the rat right ventricle using methods we have recently described (Doggrell & Vincent, 1981a). In addition the effects of 3H accumulation from (-)-[3H]-noradrenaline and on the spontaneous and field stimulation-induced overflow of 3H, following preloading of the tissue with (-)-[3H]-noradrenaline, are reported. 2 Cocaine, but not lignocaine, inhibited the accumulation of 3H from (-)-[3H]-noradrenaline. The spontaneous overflow of 3H, following preloading of the tissue with (-)-[3H]-noradrenaline was not altered by cocaine, 10 microM, or lignocaine, 100 microM. 10 microM Lignocaine had no effect on the overflow of 3H evoked by field stimulation at 5Hz. Lignocaine, 100 microM, increased and cocaine, 1 and 10 microM, reduced the decline in evoked release of 3H. This effect of lignocaine probably represents a decrease in nerve excitability and that of cocaine inhibition of neuronal uptake of noradrenaline. 3 Cocaine, 1 microM, reduced the rate of beat response to tyramine, 1 microM, alone probably by inhibiting the neuronal uptake process. 4 Cocaine, 1 and 10 microM, had no effect on the contractile responses to field stimulation (at 2 and/or 5 Hz). The rate of beat (-)-noradrenaline or (-)-isoprenaline, 1 microM, alone was decreased by cocaine, 10 microM. Lignocaine, 10 microM, reduced the force of contractions to field stimulation at 5 Hz and the responses to (-)-noradrenaline or (-)-isoprenaline alone. It is suggested that the inhibitory effects of cocaine and lignocaine on responses to (-)-isoprenaline in the rat right ventricle are due to a decreased postjunctional membrane excitability. The inability of 10 microM cocaine to potentiate contractile responses to endogenous or exogenous (-)-noradrenaline as a consequence of the inhibition of neuronal uptake is also probably due in part to decreased post-junctional excitability of the right ventricle.