Exposure of male Fischer 344 rats to an acute sound stress consisting of 100 dB tones of 2-s duration presented at random 60-s intervals for 2 h, increased cortical and midbrain tryptophan hydroxylase activity, measured in vitro, 50% over that from sham-stressed animals. This increase in enzyme activity was observed when animals were killed immediately, but not 1 h, after termination of the sound stress. It was non-additive with the increase in activity induced by incubation of enzyme under phosphorylating conditions and could be reversed in vitro with alkaline phosphatase. Graded increases in enzyme activity were obtained with increments of sound intensity (90-120 dB). In contrast to acute stress, chronic sound stress (110 dB) repeated over a period of 1, 2 or 6 weeks (3 sessions per week each of 2-h duration) produced a 50% increase in cortical enzyme activity that persisted 24 h after the termination of the stress and was not reversed by alkaline phosphatase. However, a further increase in enzyme activity could be produced if the chronically stressed animals were exposed to an acute 2-h stress (110 dB) immediately before being killed. This additional increase in activity was reversible in vitro by alkaline phosphatase and non-additive with that produced by incubation under phosphorylating conditions. In summary, acute sound stress produced a prompt, reversible activation of tryptophan hydroxylase. Repeated exposure to sound stress induced a persistent increase in enzyme activity that was detected 24 h after the last stress.