We studied 184 Cree Indian infants in randomized, prospective fashion to assess the effect of age on lymphocyte sensitization to purified protein derivative (PPD) before and after and without bacillus Calmette-Guérin (BCG) vaccination. Lymphocyte responses to PPD, Candida, and streptokinase were measured at birth and at intervals later. The mean response of paired values from 26 infants without BCG vaccination rose for the PPD stimulation index (SI) from 2.7 at birth to 3.9 before 2 yr of age. The SI for both Candida and streptokinase for this group of infants rose significantly in the first 2 yr (p less than 0.05). In 66 infants who received BCG in the first 7 days of life, the PPD-SI rose from 3.1 to 35.3 (p less than 0.001). In 17 infants who received the vaccine later but before 9 months, it rose from 3.1 at birth to 24.9, and in 14 who received it between 9 months and 2 yr, it rose from 2.2 to 52.9. The lymphocyte responses to PPD after BCG in these two groups were significantly different (p less than 0.05). There was no evidence in the older infants that a raised PPD-SI before BCG vaccination affected lymphocyte sensitization by the vaccine. We conclude that increasing the age at vaccination with BCG from birth to more than 9 months enhances immunologic sensitization to PPD significantly in this population.