Implementation of mass drug administration for lymphatic filariasis (LF) has been delayed in central Africa because of incomplete mapping and co-endemic loiasis. We mapped two regions in eastern Democratic Republic of Congo that were suspected to have LF. Night blood samples were collected from 2,724 subjects in 30 villages. Filarial antigenemia rates by card test exceeded 1% in 28 villages (range = 0–14%). Prevalence rates for large sheathed microfilariae (Mf) ranged from 4% to 40%; Mansonella perstans rates ranged from 22% to 98%. Large Mf were exclusively Loa loa by microscopy, and only 1 of 337 samples tested by quantitative polymerase chain reaction (qPCR) was positive for Wuchereria bancrofti DNA. Filarial antigen positivity was strongly associated with high L. loa Mf counts. Periodicity studies revealed atypical patterns, with no significant diurnal periodicity in some individuals. Thus, methods routinely used for LF mapping may not be reliable in areas in central Africa that are highly endemic for loiasis.