To elucidate serotonin modulation of selective attention, 13 volunteers (21-30 years) were studied in two sessions, 5 h after either acute tryptophan depletion (ATD) that decreases brain serotonin synthesis, or control-mixture ingestion (randomized, double-blind, cross-over design). Simultaneous electroencephalogram and magnetoencephalogram were measured during dichotic listening of two concurrent trains of standard and deviant tones. Subjects counted the deviants presented to one ear and ignored those presented to the other ear. ATD lowered plasma total tryptophan by 75% and free tryptophan by 39%. ATD suppressed the amplitude enhancement of P50 and N1 to selectively attended tones, but did not affect the later aspects of processing negativity. The P50 latencies were increased after ATD, irrespective of attention. In conclusion, serotonin may regulate attentional modulation of early cortical stimulus processing.