The effects of protoberberine compounds on serotonin biosynthesis in P815 cells were investigated. Protoberberine compounds such as berberine, palmatine and coralyne decreased serotonin content dose-dependently, but coptisine did not. The $IC_{50}$ values of berberine, palmatine and coralyne were $3.0;{mu}M,;16.5;{mu}M;and;14.5;{mu}M$, respectively. Protoberberine compounds at concentrations up to $20;{mu}M$ were not cytotoxic towards P815 cells. The activity of tryptophan hydroxylase, a ratelimiting enzyme in serotonin biosynthesis, was inhibited by the exposure of berberine, palmatine and coralyne in P815 cells (14.9-19.3% inhibition at $2-15;{mu}M$), but that of aromatic L-amino acid decarboxylase was not. These results suggest that the inhibition of tryptophan hydroxylase activity by berberine, palmatine and coralyne might partially contribute to the decrease in serotonin content in P815 cells.