Pyridostigmine has a protective effect against organophosphate poisoning when given in a dosage of 30 mg three times daily causing 20-40% cholinesterase inhibition. To test its safety in the human neuromuscular system, a double-blind study on 35 subjects divided into two matched groups was performed. One group was treated with pyridostigmine in a dose of 30 mg three times daily and the other group was treated similarly with placebo, both for a 10-day period. The resultant average cholinesterase inhibition in the treatment group was 23%. Muscle strength and endurance were tested before, during (on the 8th day), and after treatment. Electrodiagnostic studies, including nerve conduction, electromyography, and response to repetitive stimulation, were carried out on four subjects of the treatment group and on two subjects of the placebo group, both before and during treatment (eighth day). Isometric handgrip strength, isokinetic elbow flexor, and extensor strength did not differ between groups as a result of the treatment. Knee flexor and extensor isokinetic strength showed a small (but statistically significant) trend to improve more during placebo treatment, whereas knee extensor endurance decreased slightly in the placebo group. Both these effects are probably due to large fluctuations in performance of the placebo group, whereas the treatment group performance was quite constant. They probably do not represent any adverse effect of pyridostigmine. No electrophysiological changes were found in any of the subjects during treatment. We conclude that pyridostigmine does not cause any significant neuromuscular effect in healthy subjects when taken in a dosage of 90 mg daily for 8 days, causing 20-30% inhibition of cholinesterase.