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The transmission of Onchocerca volvulus Leuckart (Spirudida: Onchocercidae) and the prospects of Simulium neavei Roubaud (Diptera: Simuliidae) vector elimination through ground larviciding were investigated in the Mpamba–Nkusi focus, western Uganda. Transmission levels and the initiated vector elimination activities were assessed to supplement the ongoing ivermectin mass distribution programme. Searches for breeding sites, adult fly catches, dissection of flies, river treatment with temephos (Abate®) and a review of annual ivermectin treatment data were conducted. High levels of crab infestation with S. neavei sensu stricto immature stages were recorded; 57.9% and 100% for the Mpamba and Nyabugando river systems, respectively. The mean numbers of larvae/pupae per crab were 3.6 ± 0.5 in the Mpamba and 20.6 ± 1.8 in the Nyabugando systems. Pre-intervention mean biting densities were 39 and 32 flies/(man day) in 2001 and 2002, respectively, and an annual biting rate in 2001 of > 14 000. The bimodal biting pattern of S. neavei s.s. consisted of two peaks; one in the morning (09.00–10.00 hours) and one in the afternoon (14.00–15.00 hours) with a mid-day lull in biting. The infection/infective rates were 13.3%/2.8% and 16.6%/2.9% in the dissected parous flies from the Mpamba and Nyabugando river systems, respectively. Out of ∼1000 parous flies, 129 and 109 were found to be harbouring infective larvae of Onchocerca volvulus in their heads from the Mpamba and Nyabugando river systems, respectively. In spite of the > 10 years of ivermectin treatment, at a mean coverage of 71.3%, infection remained relatively high. Ground larviciding with temephos (Abate®) initiated in June and October 2002 had a significant impact. In the Mpamba river system there was a significant (P < 0.001) reduction in positive crabs from 57.9% in 2001 to 0.06% in 2003 and a decrease in the mean number of larvae/pupae per crab from 3.6 ± 0.5 in 2001 to 0.0007 ± 0.0001 (P < 0.002) in 2003. Similarly, in the Nyabugando river system, a significant (P < 0.001) reduction in crab infestation from 100% in 2001 to 0.06% in 2003 and a decrease in the mean number of larvae/pupae per crab from 20.6 ± 1.8 in 2001 to 0.06 ± 0.03 in 2003. Drastic reductions were observed in the mean number of biting flies from 3 flies/h in 2001 to 0 flies/h in 2003 and the annual biting rates fell from 14 235 flies/year in 2001 to only 730 flies/year in 2003. These data suggest that substantial progress towards the goal of S. neavei s.s. vector elimination has been made and this will enhance the ongoing ivermectin treatment in this isolated focus.