Mast cell responses were quantitated in the regional draining lymph nodes of mice during the first 24 hr after primary footpad stimulation with three concentrations each of three soluble protein antigens. The time and intensity of response varied with the type and dosage of antigen. Immunization with 50 µg of bovine serum albumin (BSA) and ferritin induced the highest mast cell responses, with peak counts five times the normal mean at 5 and 3 hr, respectively. A low antigenic dose (10 µg) of BSA or ferritin stimulated peak responses at 16 hr, and the greatest response to 7.5 µg of sulfanilazo porcine γ globulin was observed at 3 hr. At doses of 100 to 150 µg, the three antigens yielded variable results and established no definite response patterns. During peak responses the mast cells accumulated in large clusters in the interfollicular cortex and medullary regions of the nodes. No degranulation or disruption of mast cells was observed, indicating the absence of “cytophilic antibodies” on the cell surfaces. Autoradiography was employed to study the incorporation of tritiated thymidine by responding mast cells at hourly intervals through the first 24 hr after immunization. No tritium was observed in mast cell nuclei, suggesting that the mast cell responses were not due to rapid cell proliferation.