The efficacy of nine antibiotics used in different nonrandomized regimens for eradicating nasal colonization with Staphylococcus aureus was investigated in 72 patients. Dicloxacillin, erythromycin and three cephalosporins had eradicated colonization in about 75% of cases at early follow-up (less than or equal to 20 days) and in less than or equal to 50% at late follow-up (greater than or equal to 20 days). Clindamycin had eradicated colonization in all 13 patients at both follow-up times. One of two patients was successfully treated with fleroxacin, as were three of five with enoxacin. Among 21 patients treated with ofloxacin, colonization was eradicated in 20 (95%) at early follow-up and in all six of those from whom late follow-up cultures were obtained. Thus, clindamycin and ofloxacin appear to be useful systemic antibiotics for eradicating nasal colonization with Staphylococcus aureus.