Incubation of Mycobacterium bovis-sensitized bovine peripheral blood lymphocytes with concanavalin A or M. bovis purified protein derivative and indomethacin caused a consistent, statistically significant increase in [3H]thymidine uptake as compared to cultures without indomethacin. The kinetics of the response showed that indomethacin must be added to lymphocyte cultures within hours after mitogen or antigen addition for enhancement of [3H]thymidine uptake to occur. Lymphocyte blastogenic responses to purified protein derivative were enhanced in both normal and M. bovis-sensitized lymphocyte cultures. However, enhancement of sensitized lymphocyte responses was significantly (P < 0.01) greater than that in normal animals. Additionally, indomethacin treatment of M. bovis-sensitized guinea pigs significantly augmented delayed skin reactions to tuberculin. Delayed hypersensitive skin reactions were only enhanced when indomethacin was administered simultaneously with tuberculin.