The aim of our study is to evaluate the activity of antibiotics on Treponema pallidum (Tp) in the early stage of syphilis. Serum elimination kinetics for the antibiotic under study are first determined in rabbits. Four groups of seronegative rabbits are then submitted to intratesticular injection of a calibrated inoculum of Tp (Nichols virulent strain). The antibiotic is given simultaneously (TO), 3, 6 or 10 days after inoculation. Treated animals, as well as a control group of simultaneously infected untreated animals, are monitored for physical and serological changes for three months. Every animal is then tested according to the techniques of experimental rabbit syphilis to provide final conclusions. The technique investigates the direct activity on Tp of given serum concentrations of an antibiotic, and therefore the therapeutical effectiveness of an agent in a selected dosage. It also allows demonstration of sublethal activity on Tp of serum concentrations which are adequate for treating other concurrent infections (including STD) but not syphilis.