In the last decade, pyridostigmine, a quaternary carbamate that reversibly inhibits the enzyme acetylcholinesterase, was proposed for pretreatment of nerve gas (organophosphate) poisoning. The objective of this study was to assess the cardiovascular effects of pyridostigmine in patients treated with beta blockers. Eight hypertensive patients receiving regular treatment with beta blockers were randomized in a double-blind crossover study to receive pyridostigmine (30 mg 3 times daily) or placebo for 2 days. Heart rate and blood pressure in the supine and standing positions were recorded every 2 hours during the day, and 24-hour Holter monitoring was performed. In addition, a symptom-limited exercise test was performed, and plasma catecholamine levels were determined at rest and at peak exercise. Pyridostigmine, as compared with placebo, did not induce any significant effect on heart rate, plasma catecholamine levels or resting blood pressure. Both systolic and diastolic blood pressures increased in accordance with exercise intensity (p less than 0.01), although a significantly lower diastolic blood pressure was observed when pyridostigmine was used (average decrease 5 mm Hg compared with placebo; p less than 0.01). No clinical adverse reactions were observed, confirming the relative safety of the combination of low-dose pyridostigmine with beta-adrenergic blocking agents.