Two mechanisms for firing rate regulation were identified in dopaminergic nigrostriatal cells (DA cells), one of a renewal nature which prevents short and long interspike intervals (ISIs) and the other of a no-renewal nature which compensates long ISIs with short ISIs and vice versa. Renewal regulation was found in 96% of DA cells and less frequently in nigrocollicular (63%), nigrothalamic (61%) and nigropeduncular (50%) nigral GABA cells. No-renewal regulation was found in 77% of DA cells, and was only observed in 8% of GABA cells. Thus, most DA cells showed both regulatory mechanisms, which justifies the low variability in their firing rate and the low oscillation of extracellular striatal dopamine previously reported. DA cells surviving a partial degeneration of the nigrostriatal system did not show alterations in their firing rate and burst firing but presented a marked disturbance for no-renewal regulation. Under these conditions, small fluctuations in firing rate are not compensated for in time, which could be one of the factors responsible for the motor fluctuations often observed in advanced Parkinson's disease.