We have examined the idea that the adaptation of cortical neurons to local contrast levels in a visual stimulus is functionally advantageous. Specifically, cortical cells may have large differential contrast sensitivity as a result of adjustments that center a limited response range around a mean level of contrast. To evaluate this notion, we measured contrast-response functions of cells in striate cortex while systematically adapting them to different contrast levels of stimulus gratings. For the majority of cortical neurons tested, the results of this basic experiment show that contrast-response functions shift laterally along a log-contrast axis so that response functions match mean contrast levels in the stimulus. This implies a contrast-dependent change in the gain of the cell's contrast-response relationship. We define this process as contrast gain control. The degree to which this contrast adjustment occurs varies considerably from cell to cell. There are no obvious differences regarding cell type (simple vs. complex) or laminar distribution. Contrast gain control is almost certainly a cortical function, since lateral geniculate cells and fibers exhibit only minimal effects. Tests presented in the accompanying paper (37) provide additional evidence on the cortical origin of the process. In another series of experiments, the effect of contrast adaptation on physiological estimates of contrast sensitivity was evaluated. Sustained adaptation to contrast levels as low as 3% was capable of nearly doubling the thresholds of most of the cells tested. Adaptation may therefore be an important factor in determinations of the contrast sensitivity of cortical neurons. We tested the spatial extent of the mechanisms responsible for these gain-control effects by attempting to adapt cells using both a large grating and a grating patch limited to that portion of a cell's receptive field from which excitatory discharges could be elicited directly (the central discharge region). Adaptation was found to be an exclusive property of the central region. This held even in the case of hypercomplex cells, which received strong influences from surrounding regions of the visual field. Finally, we measured the time course of contrast adaptation. We found the process to be rather slow, with a mean time constant of approximately 6 s. Once again, there was considerable variability in this value from cell to cell.