The frequency of spontaneous synaptic events in vitro is probably lower than in vivo because of the reduced synaptic connectivity present in cortical slices and the lower temperature used during in vitro experiments. Because this reduction in background synaptic activity could modify the integrative properties of cortical neurons, we compared the impact of spontaneous synaptic events on the resting properties of intracellularly recorded pyramidal neurons in vivo and in vitro by blocking synaptic transmission with tetrodotoxin (TTX). The amount of synaptic activity was much lower in brain slices (at 34 degrees C), as the standard deviation of the intracellular signal was 10-17 times lower in vitro than in vivo. Input resistances (Rins) measured in vivo during relatively quiescent epochs ("control Rins") could be reduced by up to 70% during periods of intense spontaneous activity. Further, the control Rins were increased by approximately 30-70% after TTX application in vivo, approaching in vitro values. In contrast, TTX produced negligible Rin changes in vitro (approximately 4%). These results indicate that, compared with the in vitro situation, the background synaptic activity present in intact networks dramatically reduces the electrical compactness of cortical neurons and modifies their integrative properties. The impact of the spontaneous synaptic bombardment should be taken into account when extrapolating in vitro findings to the intact brain.