To define the clinical spectrum of loiasis more precisely and to begin to assess the immunologic basis for the difference in clinical manifestations between visitors to endemic areas and natives of these areas, 51 West African patients with loiasis were evaluated and compared with 42 infected expatriates. Microfilaremia was present in 90% and Calabar swellings in only 16% of the endemic patients. Conversely, only 10% of the expatriates were microfilaremic while 95% complained of Calabar swellings. The endemic population showed significantly decreased levels of peripheral blood eosinophils, parasite-specific IgG, and lymphocyte proliferation to parasite antigens compared with the nonendemic population. These findings support the hypothesis that differences in the modulation of the immune response to parasite antigen are responsible for the observed differences in clinical presentation between expatriate and endemic populations with loiasis.