Vasoactive intestinal peptide-expressing (VIP) interneurons in the cortex regulate feedback inhibition of pyramidal neurons through suppression of somatostatin-expressing (SST) interneurons and, reciprocally, SST neurons inhibit VIP neurons. Although VIP neuron activity in the primary visual cortex (V1) of mouse is highly correlated with locomotion, the relevance of locomotion-related VIP neuron activity to visual coding is not known. Here we show that VIP neurons in mouse V1 respond strongly to low contrast front-to-back motion that is congruent with self-motion during locomotion but are suppressed by other directions and contrasts. VIP and SST neurons have complementary contrast tuning. Layer 2/3 contains a substantially larger population of low contrast preferring pyramidal neurons than deeper layers, and layer 2/3 (but not deeper layer) pyramidal neurons show bias for front-to-back motion specifically at low contrast. Network modeling indicates that VIP-SST mutual antagonism regulates the gain of the cortex to achieve sensitivity to specific weak stimuli without compromising network stability.