This study was designed to examine the effects of tetracycline on DNA and protein synthesis by human lymphocytes treated with Con A. The effects of the drug were also assessed in terms of the in vitro production of the lymphokine, migration inhibitory factor (MIF). The results indicate that marked suppression of protein synthesis occurred in presence of tetracycline at all concentrations including clinically achievable doses. The group mean values of DNA synthesis did not show significant inhibition with lower concentrations of the drug. The marked decline in protein synthesis in tetracycline treated cultures was accompanied by a significant suppression of MIF production. Accelerated migration of macrophages was observed when the lymphocyte supernatant was produced in presence of the higher concentrations of tetracycline (75-100 microliter/ml). These observations suggest that tetracycline interfered with the in vitro correlates of cellular immunity in humans. This raises a possibility that indiscriminate use of the drug might compromise host defenses especially where long-term therapy is prescribed.