It is not known whether the variability of neural activity in the cerebral cortex carries information or reflects noisy underlying mechanisms. In an examination of the reliability of spike generation using recordings from neurons in rat neocortical slices, the precision of spike timing was found to depend on stimulus transients. Constant stimuli led to imprecise spike trains, whereas stimuli with fluctuations resembling synaptic activity produced spike trains with timing reproducible to less than 1 millisecond. These data suggest a low intrinsic noise level in spike generation, which could allow cortical neurons to accurately transform synaptic input into spike sequences, supporting a possible role for spike timing in the processing of cortical information by the neocortex.