Following the registration of ivermectin (Mectizan®) for human use in the treatment of onchocerciasis, in 1987 the Onchocerciasis Control Programme in West Africa (OCP) begun a series of trials in order to determine the safety of the drug when used on a large scale and its potential for morbidity control. This paper reports the changes in skin microfilarial loads during the first 5 years of annual treatment in the holoendemic focus of Asubende in Ghana, which was the largest trial area and which also had the longest series of followup surveys. The general observed pattern was a marked reduction of microfilarial loads shortly after each treatment followed by a steady repopulation of the skin until a subsequent treatment round. The overall reduction of microfilarial loads observed between the base line survey and one year after the last treatment was 90% for the total population examined and over 93% for a cohort which received the drug at all 5 treatment rounds. In contrast, there was only a very gradual decrease in the prevalence of infection in the population after subsequent treatments. The study further emphasizes that even a single treatment with ivermectin has a significant medium-term impact on microfilarial loads. Microfilarial counts barely increased after 14–16 months of treatment and stabilized around 55% of pre-treatment counts 2–4 years after a single treatment.