The effect of scopolamine hydrobromide (0.4 mg s.c.) on spontaneous yawning was studied in 16 male volunteers in a double-blind study. Scopolamine (or placebo) was given 60 min before (–60 min) placebo (physiological saline s.c.) (time 0 min) and yawning monitored from –15 to +60 min by recording displacement of the lower jaw and storing the traces on diskettes. After placebo, the number of yawns was 5.3 ± 1.4 (X ± SE) and after scopolamine pretreatment 4.3 ± 1.6 (p = NS). Drowsiness was assessed with the Stanford Sleepiness Scale and the Analog Sleepiness Scale at –15,0, +20, +40, +60 min. There was no significant correlation between total sleepiness scores (area under the curve, 0 min to +60 min), peak sleepiness score or peak increment in sleepiness score and number of yawns on either scale. These data suggest that (a) spontaneous yawning in man is not mediated by a central muscarinic cholinergic link, and (b) the assumed relationship between drowsiness and yawning remains to be verified experimentally.