We studied the cardiovascular effect of 0.5 mg of arecoline, a centrally active cholinergic muscarinic agonist, infused over a 3-minute period during the second non-REM (rapid-eye-movement) sleep cycle in 23 patients with major depression. A clear-cut cardioacceleratory response, beginning at the second minute of the 3-minute infusion, and reaching a peak about 5-6 minutes from the start of the infusion, was noted. Placebo infusion did not alter heart rate. There was a significant correlation between the magnitude of the heart rate increase and the latency to onset of the second REM period after arecoline infusion (-0.49). Neither baseline nor arecoline-induced heart rate increases were related to age, sex, or sleep stage changes during or following arecoline infusion. Our data suggest the use of the cardioacceleratory response to cholinomimetics as an additional research tool in assessing central cholinergic sensitivity in humans, especially in neuropsychiatric and stress-related states where cholinergic alterations may occur.