Mucosal mast cell numbers are modulated in the intestines of rodents during parasitic infections. These mast cells can degranulate in response to worm antigens, and this event has been suggested to play a protective role for the host. To examine whether mast cells in higher animals play a role in protecting from disseminated parasitic disease, mast cell numbers and responsiveness to parasite antigens were evaluateed in 5 Erythrocebus patas infected with the human intestinal nematode Stronglyoides stercoralis. Initial infection and subsequent challenge infections were associated with increases in jejunal histamine and mast cell numbers, and these mast cells could release histamine in response to parasite antigens. Jejunal mast cell numbers returned to normal during a chronic phase of infection. The cells lost their ability to respond to antigenic stimulation following limited steroid treatment. Subsequent activation of chronic infections to fatal disseminated disease by more prolonged steroid treatment was associated with a marked decrease in jejunal mast cell numbers and histamine. In one animal which succumbed to severe disease without steroid treatment, jejunal mast cells were refractory to worm antigens.