Inhibition of nucleus accumbens neurons is hypothesized to be a mechanism that contributes to the reinforcing (addictive) effects of cocaine and other drugs. To test this hypothesis, the activity of single nucleus accumbens neurons of rats was recorded extracellularly during cocaine self-administration sessions. Fifty-eight percent of neurons were tonically inhibited during cocaine self-administration relative to predrug baseline; thirty-one percent were tonically excited. A majority of both excited and inhibited neurons showed phasic increases in firing time-locked to self-infusion. The high percentage of tonically inhibited neurons is in line with the strong inhibitory effects of cocaine and amphetamine observed in previous anesthetized and slice recording studies; however, the prevalence of inhibition, relative to excitation, was less than might have been expected on the basis of the earlier recording studies. The present results support the hypothesis that accumbal (tonic) inhibition contributes to drug taking. However, they also suggest that changes in firing that are distinct from the tonic inhibition may additionally contribute to accumbal mediation of drug taking and drug addiction. The uniform observation of predominant inhibition among the various electrophysiology studies is consistent with the heuristic value of anesthetized and slice recording methods in identifying potential neurophysiological correlates of drug taking; however, the existence of firing patterns (e.g., phasic increases) uniquely associated with self-administration behavior (and thus absent in anesthetized and slice studies), as well as the unique presence of the primary behavior of interest in studies such as the present one, underscores the importance of conducting electrophysiological investigations of drug taking and drug addiction in the self-administering animal in parallel with anesthetized and slice studies whenever possible.