The direct effects of the neurotransmitter serotonin on the catecholaminergic enzyme, tyrosine hydroxylase and the microtubule-associated tau protein were studied in a human neuroblastoma cell line. Undifferentiated LAN-5 cells, cultured in serum supplemented basal medium, or cells induced to differentiate by 6 day exposure to 10 uM retinoic acid were treated for 48 hr with 50 nM and 50 uM serotonin. In undifferentiated cells, serotonin treatment (50 uM) decreased both tyrosine hydroxylase activity and a 50 kD cytoplasmic fraction tau protein while 50 nM serotonin treatment caused this 50 kD protein to increase in the cytoplasmic fraction but decrease in the membrane fraction. While basal tyrosine hydroxylase activity increased in differentiated vs. undifferentiated cells, serotonin treatment had no effect on the enzyme or tau in differentiated LAN-5. This study shows serotonin to have direct effects on the biochemistry and cytoskeleton of undifferentiated cultured human neuroblastoma.