We report that the mRNAs of two serotonin receptor subtypes, 5-HT1B and 5HT2A, are specifically expressed in the primary visual cortex (V1) of macaque monkeys and that the strength of expression is controlled in an activity-dependent manner. To elucidate functional roles of these receptors in vivo, we performed electrophysiological recordings of visual responses from 101 V1 neurons with microiontophoretic administration of specific drugs for each receptor subtypes in anesthetized and paralyzed monkeys. The effects of activating these receptors seemed to be bidirectional depending on the activity levels of each neuron. The effect of agonist for 5-HT1B receptor, CP93129, was more facilitatory when the firing rate was high, but the effect was more suppressive when the firing rate was low. The effect of DOI, agonist for 5-HT2A receptor, was opposite in direction. That is, the effect of DOI was more suppressive when the firing rate was high, but more faciliatatory when the firing rate was low. Highly restricted expressions of these receptors and their neural-activity-dependent actions in V1 suggest that 5-HT1B and 5-HT2A receptors complementarily control the gain of input-output relation of V1 with an activity-dependent manner, which could modulate further processing in the cortical network. [J Physiol Sci. 2007;57 Suppl:S100]