The effects of harmaline, an indoleamine and a MAOI, were tested on the acoustic startle pattern. EMG measures of the startle reflex, the pinna reflex as well as the characters of the vertex evoked responses to brief intense tone bursts (60 msec, 110 dB, 8000 Hz) were simultaneously studied in 4 alert guinea-pigs. The basic experimental design was a 4 by 4 latin square, with the treatments being given at 2 day intervals. The four harmaline-HCl treatments were isotonic saline, 0.25, 5.0, and 10.0 mg/kg. Compared with saline baselines, all the doses resulted, throughout the 60 min session, in overall high significant depressions of the startle reflex, the pinna reflex and the initial wave of the acoustic evoked potential at the vertex. In contrast, harmaline had little or no influence on amplitude and latency of the late wave of the vertex response. The effects of harmaline on the general behavior of the guinea-pig are also reported. These results may support an involvement of serotonergic systems in the modulation of the sensory-motor reactivity at the brainstem level. Nevertheless, the probably more complex cortical processes involved in startle responsiveness do not appear univocally affected by the indoleamine drugs such as harmaline.