Diethylcarbamazine (DEC) therapy for Onchocerca volvulus infection results in frequent ocular and systemic complications, but the pathogenesis of these complications is unclear. Twenty men with O. volvulus infection were treated over a period of six months with DEC given daily for one week and weekly thereafter. Major systemic and ocular complications included proteinuria, severe pruritus, visual field constriction, optic nerve pallor, chorioretinitis, anterior uveitis, and punctate keratitis. Levels of circulating immune complexes (CICs) were increased (greater than 11% [125I]C1q binding) in 14 of the 20 men prior to treatment. Persons with pretreatment C1q binding activity of greater than 30% were at increased risk to develop constriction of visual fields (P less than 0.05) and proteinuria (P less than 0.015). Linear regression analysis revealed a striking correlation between pretreatment levels of CICs and the total number of both systemic and ocular complications (P less than 0.001) and ocular complications alone (P less than 0.005). These results suggest that CICs may be important in the pathogenesis of the delayed systemic and ocular complications following DEC therapy for O. volvulus infection.