Cefmetazole, a cephamycin-type antibiotic, was shown to be as effective as standard benzathine penicillin for therapy of active syphilis in the rabbit model. Four groups of six adult male rabbits were inoculated intradermally with 10(6) Treponema pallidum per site, producing primary syphilitic lesions. One week following infection, groups of rabbits were treated with benzathine penicillin (200,000 U intramuscularly weekly for 2 weeks) or cefmetazole (20 or 40 mg/kg per day intramuscularly in four divided doses for 15 days); one group was untreated. Daily dark-field microscopic examination of lesion aspirates demonstrated that the mean times to dark-field negativity were the same for benzathine penicillin- and two cefmetazole-treated groups (1.0. 1.0, and 1.17 days, respectively), while all untreated animals remained dark-field positive for greater than 15 days. Mean maximum lesion diameters in cefmetazole-treated animals (8.7 +/- 1.3 and 8.1 +/- 1.3 mm) were equivalent to those in penicillin-treated animals (8.6 +/- 1.6 mm) and were smaller than observed in untreated animals (12.4 +/- 2.2 mm; P less than 0.01); fewer lesions ulcerated in penicillin- or cefmetazole-treated rabbits than in untreated rabbits (P less than 0.001). Persistent infection was documented in lymph nodes of untreated rabbits; no evidence of latent infection was found in penicillin- or cefmetazole-treated animals.