During a critical period of postnatal development, neuronal connections in the kitten visual cortex are susceptible to experience-dependent modifications. These modifications are facilitated by the neuromodulators noradrenaline and acetylcholine. To address the question of whether serotonin (5-hydroxytryptamine; 5-HT), the other major neuromodulator in the cerebral cortex, also plays a role in developmental plasticity, we investigated whether interference with serotoninergic transmission in the kitten visual cortex affects ocular dominance (OD) plasticity. The serotonin neurotoxin 5,7-dihydroxytryptamine or the serotonin receptor blockers ketanserin and methysergide were infused into the visual cortex of kittens undergoing monocular deprivation. We found that both methods of disrupting serotoninergic transmission reduced OD plasticity. However, to be effective, the receptor blockers ketanserin and methysergide had to be applied in combination, suggesting that coactivation of serotonin receptor subtypes of both the 5-HT1 and 5-HT2 families have a permissive function in OD plasticity. Since activation of 5-HT2 receptors stimulates phosphoinositide hydrolysis, our data suggest that second messengers from the phospholipid pathway may play an important role in developmental plasticity of visual cortex.