In this study, we investigated the functional impact of interhemispheric projections on neurons in their target zones. Electrophysiological recordings were performed in primary visual areas 17 and 18 of the anesthetized cat. We combined the electrophysiological recordings with reversible cooling deactivation. Our results demonstrate a stimulus specific modulation of firing rates in the callosal recipient zone, with a predominant excitatory influence. The effects could be observed for static and moving stimuli and persisted throughout the stimulation period. Additionally, spontaneous activity was affected in a similar way. We also characterized the mechanism of those modulations, revealing a multiplicative scaling, especially for those cells which show a strong change in spike rate at their preferred direction. Tuning width was only faintly influenced by the callosal fibers, but a correlation existed between the additive component of amplitude scaling and a small change in tuning width. According to previous experimental and theoretical work, we created a simple model of response modulation of tuning curves. Those simulations indicated that a multiplicative scaling of tuning curves can be obtained by the addition of cortico-cortical synaptic input to the membrane potential, in the presence of a nonlinear input-output transformation or by tuned synaptic input. Furthermore, we estimated neuronal discharge variability, including trial-to-trial variability measured by the Fano factor and within trial variability, or spiking noise, measured by the coefficient of variation. We found a stimulus-dependent change for both measures, with a more pronounced decrease in trial-to-trial variability compared to spiking noise. A strong decrease in trial-to-trial variability was mainly present in neurons which increased their spike rate during cooling deactivation. The profound effects of cooling on trial-to-trial variability point towards a modulation of ongoing fluctuations by callosal or lateral connections. These fluctuations are added to the stimulus induced responses. Our results complete the view of how cortico-cortical connections in the brain shape responses to external stimuli and are in line with previous work on the physiological role of feedback projections and callosal connections. They provide, for the first time, an extensive evaluation and mathematical description of the contributions of long-range projections to the response properties of cortical neurons. Furthermore, they demonstrate that what we usually call “noise”, and try to get rid of by extensive averaging, is indeed part of the system and might be dynamically regulated. Therefore, in understanding more complex features of visual processing, like center-surround interactions or scene segmentation, it might be important to consider the variability of neuronal actions and interactions. Indeed, over the last view years it became clear that neuronal variability in a variety of cortical areas plays a critical role in conscious perception and motor actions. Finally, our results have implications for neuronal coding, showing that cortico-cortical connections can alter the rate and timing of spikes.