The ability of the macrolide antibiotic azithromycin and its epimer CP-63,956 to inhibit protein synthesis in two pathogenic strains of Treponema pallidum was investigated. Using an in-vitro radiolabelling procedure employing treponemes freshly extracted from infected rabbit testes, our results indicate that both antibiotics were comparable with erythromycin in their ability to inhibit protein synthesis in T. pallidum Nichols strain. An erythromycin-resistant clinical isolate of T. pallidum, designated Street strain 14, exhibited only partial inhibition of protein synthesis at the highest antibiotic concentration tested.