The side effects of chronic pyridostigmine bromide administration were studied in seven male soldiers performing moderate-intensity exercise in a desert environment. A 2-week, double-blind, placebo-controlled crossover design was employed in which pyridostigmine was administered for 7 consecutive days (30 mg orally, t.i.d.). Four hours each day were spent in the heat (42 degrees C, 20% relative humidity); 2 hours rest followed by 2 hours moderate exercise (40% maximal aerobic power). Each day, subjects completed four symptom questionnaires and received three focused physical examinations. Symptoms reported did not differ between treatment groups except for fewer headaches during pyridostigmine treatment. Soldiers were unable to distinguish the effects of pyridostigmine from placebo. Pyridostigmine was associated with lower resting diastolic blood pressure (approximately 4 mmHg, p less than 0.05), smaller pupil diameter (approximately 0.5 mm, p less than 0.01), decreased handgrip strength (approximately 3%, p less than 0.05), and higher final rectal temperature (approximately 0.1 degree C, p less than 0.01). Effects of this magnitude are not likely to appreciably limit performance. We conclude that chronic pyridostigmine administration does not negatively impact on soldiers' ability to perform physical work over repeated days in a desert environment.