Hundreds of thalamic axons ramify within a column of cat visual cortex; yet each layer 4 neuron receives input from only a fraction of them. We have examined the specificity of these connections by recording simultaneously from layer 4 simple cells and cells in the lateral geniculate nucleus with spatially overlapping receptive fields (n = 221 cell pairs). Because of the precise retinotopic organization of visual cortex, the geniculate axons and simple-cell dendrites of these cell pairs should have overlapped within layer 4. Nevertheless, monosynaptic connections were identified in only 33% of all cases, as estimated by cross-correlation analysis. The visual responses of monosynaptically connected geniculate cells and simple cells were closely related. The probability of connection was greatest when a geniculate center overlapped a strong simple-cell subregion of the same sign (ON or OFF) near the center of the subregion. This probability was further increased when the time courses of the visual responses were similar. In addition, the connections were strongest when the simple-cell subregion and the geniculate center were matched in position, sign, and size. The rules of connectivity between geniculate afferents and simple cells resemble those found for retinal afferents to geniculate cells. The connections along the retinogeniculocortical pathway, therefore, show a precision that goes beyond simple retinotopy to include many other response properties, such as receptive-field sign, timing, subregion strength, and size. This specificity in wiring emphasizes the need for developmental mechanisms (presumably correlation-based) that can select among afferents that differ only slightly in their response properties.