Hygienic self-grooming is a behavioral adaptation for removing litter particles and pathogenic agents from animal fur and skin. We studied contribution of brain serotonin system into mechanisms regulating hygienic behavior in intact mice and mice with LPS(lipopolysaccharide)-induced sickness. A spot of fluorescent dye was applied on the back of a mouse, and the decrease in its fluorescence served as an index of fur cleaning efficiency estimated using original classifier algorithm. Agonist of 5-HT(1A) receptor (8-OH-DPAT) or 5-HT(2A/2C) receptor (DOI) attenuated fur cleaning at a dose of 1 mg/kg but not of 0.2 mg/kg. MAO-A inhibitor clorgyline decreased hygienic self-grooming at a dose of 10 but not of 5 mg/kg. SSRI paroxetine had no effect while fluoxetine diminished hygienic behavior at the higher dose used (20 mg/kg). Inhibitory effect of LPS treatment (50 Âµg/kg) on fur cleaning was not altered by administration of p-MPPI (5-HT(1A) receptor antagonist, 1mg/kg) or DOI (1mg/kg) while 8-OH-DPAT (1 mg/kg) produced additive effect. The results suggest the involvement of 5-HT(1A) and 5-HT(2A/2C) brain serotonin receptors and MAO-A in the inhibition of hygienic behavior in mice. However, LPS-induced depression of fur cleaning appeared to be mediated via different mechanisms and enhanced by 5-HT(1A) receptor activation.