Guinea pigs immunized with bacillus Calmette-Guérin (BCG) and rendered pyridoxine-deficient by dietary means or by treatment with deoxy-pyridoxine (DB6) showed severely depressed systemic reactivity to purified protein derivative (PPD) although in vitro sensitivity of certain spleen cells could be demonstrated. This is in agreement with the results on skin sensitivity. The use of killed BCG to sensitize a group of these animals demonstrates that interference with proliferation of this organism by pyridoxine deficiency of the host is not a dominant factor in depression of reactivity. The deficient animals showed no change in anaphylactic reactivity. Vitamin C deficiency and inanition due to low food intake did not result in depression of reactivity. It appears that pyridoxine deficiency may interfere with a step in the reaction between sensitized cells and the allergen.