We used autoradiography to examine the extent of reversible inactivation produced by microinjection of lidocaine (40 micrograms/microliters saline) and muscimol (1 microgram/microliter saline). We measured intracortical spread of tracer amounts of labelled drug and local changes in uptake of [1-14C]glucose produced by the microinjection. The maximal average radii of regions of drug spread were 1.7 mm for both [14C]lidocaine and [3H]muscimol and were achieved within the first 20 min postinjection. The width of lidocaine injections decreased at longer postinjection times (30-60 min) but the width of muscimol injections remained relatively constant (30-120 min). Lidocaine radioactivity decreased faster from the injection site than muscimol radioactivity. Glucose autoradiograms showed a discrete region of maximally reduced glucose uptake (1.4 mm for lidocaine and 1.0 mm for muscimol) surrounded by a region of less reduced glucose uptake (up to approximately 3 mm). These findings suggest that, in the cortex, the effects of focal inactivation extend beyond the region of drug spread. Diffuse effects may be mediated of disfacilitation of cortico-cortical circuits.