Cocaine is a natural alkaloid, which affects excitability of dopaminergic pathways, and may be able to "hijack" the endogenous reward system. The relationships between cocaine-induced behaviour and its action on the excitability of dopaminergic (and other) neurons are not clear. We investigated the effects of cocaine on the firing of midbrain dopaminergic (DA) neurons, both in anaesthetized (n = 7) and in freely moving (n = 13) Wistar rats, using pre-implanted multielectrode arrays and a recently developed telemetric recording system (Alpha-Omega, Israel). During the experiment, animals received intraperitoneal injections of saline or cocaine (10 mg/kg). To observe the effects of general anaesthesia on the activity of recorded units, 4 animals from the awake group were anaesthetized with chloral hydrate in the second part of the recording session. We also measured plasma and brain concentrations of cocaine and its main metabolite, benzoylecgonine, at the 10th or 30th minute after the cocaine injection. Average baseline activity of DA neurons consisted of irregular tonic firing interrupted by bursting periods. Injection of saline did not lead to any significant change in the firing of these neurons. After the injection of cocaine in awake rats (n = 52), we observed in a large population of DA neurons (n = 19, 37%) a gradual increase in firing rate and bursting which was not time-locked to the locomotor activity of the animals. In other DA neurons, such increases were time-locked to the locomotor activity (n = 23, 44% of the cells). In anaesthetized animals cocaine produced a general decrease of the firing rate and bursting of DA neurons (n = 27), sometimes preceded by a transient increase in both parameters. In particular, monotonous increases observed in awake animals were not observed in these conditions. Injection of chloral hydrate in awake rats induced an inhibitory effect in 7 out of 10 recorded presumably DA units. This can partly explain the difference between awake and anaesthetized groups. Measured brain cocaine and benzoylecgonine concentrations suggested that differences observed in electrophysiological experiments did not have a pharmacokinetic origin. Taken together, our results demonstrate that cocaine injection differentially affects the electrical activity of DA neurons in awake and anaesthetized rats. These observations show that electrophysiological recordings in awake animals allow to uncover changes in neuronal excitability in the presence of an exogenous agent that are absent in anaesthetized animals.