Spontaneous diminution of granuloma formation around schistosome eggs in chronic schistosomiasis mansoni has been demonstrated previously. In the present study these findings were confirmed by injecting schistosome eggs into the pulmonary microvasculature and removing the lungs 8 days later from mice infected for 4, 8, 12, 16, and 20 weeks; the mean area of inflammation around the eggs was then measured. At 4 weeks a primary reaction was seen, by 8 weeks a massive secondary reaction occurred, but by 12 weeks the lesion was considerably reduced in size, and at 20 weeks it was smaller than the primary reaction. Concomitant measurements of humoral hemagglutinins to soluble egg antigens (SEA) revealed no detectable antibodies at 4 and 6 weeks, relatively low levels at 8 weeks, and an exponential increase in hemagglutinins at 12 weeks and beyond. Immunodiffusion analysis revealed no precipitins at 8 weeks, 1 major band and 2 minor bands at 12 and 16 weeks, and 2 major bands and 1 minor band at 20 weeks. Spleen cells from 8-week-infected mice showed peak migration inhibitory factor (MIF) output at a concentration of 1 mug/ml of soluble egg antigens and suppression of lymphokine secretion at higher concentrations. At 12 and 16 weeks, exponentially lower antigen concentrations both stimulated and suppressed peak MIF output; at 20 weeks MIF was not detectable after stimulation over a wide range of antigen concentrations. Delayed footpad swelling to SEA reached its peak at 10 weeks and declined thereafter, but the response to PPD in tuberculin-sensitized schistosome infected mice remained constant over the period of time studied.