Rationale: Various studies have demonstrated a modulating role for serotonin in attention. Selective serotonin inhibitors have repeatedly been shown to impair performance in sustained attention tasks. Objectives: To assess the contribution of serotonin reuptake inhibition and specific blockade of the pre-synaptic 5-HT1a receptor and the 5-HT2a receptor to deficits in attention. Materials and methods: The study was conducted according to a randomized, double-blind, placebo controlled, four-way crossover design including 16 healthy volunteers. Treatments consisted of oral administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram 20 mg + placebo; escitalopram 20 mg + ketanserin (5-HT2a antagonist), 50 mg; escitalopram 20 mg + pindolol (5-HT1a antagonist) 10 mg; and placebo + placebo on four separate days. A range of performance tasks were conducted to assess the subjects' attention and motor functions. Results: Escitalopram administered alone impaired tracking performance in a divided attention task. The combination of escitalopram and pindolol and escitalopram and ketanserin impaired divided attention as compared to placebo. In addition, escitalopram and ketanserin impaired sustained attention. Divided attention impairment observed after combined treatments did not significantly differ from impairments after escitalopram alone. Sustained attention impairment observed after combined escitalopram and ketanserin significantly differed from escitalopram alone. Conclusions: 5HT(1a) blockade hardly affected SSRI effects on attention. Additional 5HT(2a) blockade, however, produced impairments of sustained attention and motor impulse control.