Microdialysis is a useful tool for administering drugs into localized regions of brain tissue, but the diffusion of drugs from the probe has not been systematically examined. Lidocaine (10%) and tetrodotoxin (TTX, 10 microM), drugs typically used in neural inactivation studies, were infused through a microdialysis probe into raccoon somatosensory cortex while evoked responses were recorded at four electrodes equally spaced 0.5--2.0 mm from the probe. The decreases in evoked response amplitude as a function of time and distance from the probe were used as functional measures to describe the time course and spread of the drugs. TTX inactivated distant sites more quickly and to a greater extent than lidocaine. Responses recovered within approximately 40 min after termination of lidocaine, but did not recover for at least 2 h after TTX. Based on these measurements, we estimated that, at the concentrations used, lidocaine has a maximal spread of 2.1 mm, while TTX could spread as far as 4.8 mm from the microdialysis probe. However, in terms of significant inactivation of neuronal activity, lidocaine and TTX have an effective spread of 1 and 2 mm, respectively.