The aim of this study was the evaluation of some parameters which might better characterize ciprofloxacin: the influence of inoculum, serum and medium. Resistance development, hamster protection and mycoplasmacidal concentrations were also investigated. Ciprofloxacin showed moderate antimycoplasmal activity, both in vitro and in vivo. The minimum inhibitory concentrations (MICs) for Ureaplasma urealyticum, if compared to those shown by erythromycin, are lower, but higher than those obtained with tetracyclines. Unlike the macrolides, ciprofloxacin suffers from change of inoculum size, but no single step resistance induction was reported both in ureaplasmas and mycoplasmas. If Mycoplasma pneumoniae pneumonia or genital infections due to U. urealyticum carry out gram-negative rod isolation, ciprofloxacin can be considered a valid therapeutic agent for these mixed infections.