Thirty-four healthy adult males, moderately to heavily infected with Onchocerca volvulus, were treated daily with metrifonate at 10 mg/kg body weight for either three or six days. The patients' reactions and the effects on the microfilariae were measured on a 'single-blind' basis. Muscarinic effects of acetylcholine were prominent despite the use of belladonna alkaloids, and nicotinic effects--leading to a proximal muscle weakness--occurred in one patient after the fifth dose. A syndrome of polyarthritis, fever and elevated erythrocyte sedimentation rate occurred in 11 patients, in two of whom microfilariae were demonstrated in the joint fluid. The six-day regime destroyed 83% of the microfilarial load and the three-day regime destroyed 72%, but the difference was not statistically significant (as assessed one week after the completion of treatment). It seems unlikely that metrifonate will replace DEC as the 'reference' microfilaricide and attempts to improve its efficacy by employing higher dosage must employ an intermittent dose regime.