The numbers of eosinophils and mast cells observed at the tumor border of 331 rectal cancers from patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP), protocol R-01, were correlated according to overall survival rate, as well as Dukes' stage, tumor differentiation, nodal status, degree of lymphoid and stromal reactions, sex, and age. Life table plots disclosed a significantly better overall survival rate when ten or more eosinophils per 30 oil immersion fields were found. However, the numbers of eosinophils were strongly associated with Dukes' stage and, when life table plots were adjusted for Dukes' stage, this relationship to survival rate was not evident. On the other hand, overall survival rate was significantly higher in patients in whom 0 to three mast cells per 30 oil immersion fields were found than in those patients in whom four or more mast cells were found. This relationship persisted even when life table plots were adjusted for treatment, Dukes' stage, or nodal status, and indicated that the number of mast cells further defined survival rate among patients exhibiting Dukes' A, B, and C stages. It is concluded that numbers of eosinophils and mast cells may play a role in the natural history of rectal cancer but only the latter represents a prognostic parameter independent of Dukes' stage or nodal status. The mechanism whereby mast cells may exert this effect is at present unknown.