Center-surround antagonism is a hallmark feature of the receptive fields of sensory neurons. In retinas of lower vertebrates, surround antagonism derives in part from inhibition of cone photoreceptors by horizontal cells. Using whole-cell patch recording methods, we found that light-evoked responses of cones in macaque monkey were antagonized when surrounding cones were illuminated. The spatial and spectral properties of this antagonism indicate that it results from inhibition by horizontal cells. It has been suggested that horizontal cell inhibition is mediated by the neurotransmitter GABA. The inhibition observed here, however, was inconsistent with a GABA-gated chloride conductance mechanism. Instead, surround illumination evoked an increase in calcium conductance and calcium-activated chloride conductance in cones. We expect that these conductances modulate neurotransmitter release at the cone synapse and increase visual sensitivity to spatial contrast.