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They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> stimulation activates affective processing brain regions, alluding to their role in affective touch perception. We tested a theory that <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010activating touch engages the pro\u2010social functions of serotonin, by determining whether reducing serotonin, through acute tryptophan depletion, diminishes subjective pleasantness and affective brain responses to gentle touch. A tryptophan depleting amino acid drink was administered to 16 healthy females, with a further 14 receiving a control drink. After 4\u00a0h, participants underwent an <jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content> scan, during which time <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010innervated forearm skin and <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> non\u2010innervated finger skin was stroked with three brushes of differing texture, at <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010optimal force and velocity. Pleasantness ratings were obtained post scanning. The control group showed a greater response in ipsilateral orbitofrontal cortex to <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010activating forearm touch compared to touch to the finger where <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>s are absent. This differential response was not present in the tryptophan depleted group. This interaction effect was significant. In addition, control participants showed a differential primary somatosensory cortex response to brush texture applied to the finger, a purely discriminatory touch response, which was not observed in the tryptophan depleted group. This interaction effect was also significant. Pleasantness ratings were similar across treatment groups. These results implicate serotonin in the differentiation between <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010activating and purely discriminatory touch responses. 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