We investigated a new oral cephem antibiotic, cefotiam hexetil (CTM-HE), a pro-drug of cefotiam (CTM), for its clinical efficacy and safety. Cefotiam hexetil was administered in 100-400 mg doses ...postprandially three times a day to 145 patients with various skin infections for 3 to 28 days. Clinical response was excellent or good in 134 cases, and the efficacy rate was 93.1%. One case with erythma nodosum was not assessed. The MIC of CTM for 56 clinically isolated strains of Staphylococcus aureus was 0.2-3.13μg/ml (106cfu/ml). The bacteriological effect on S. aureus was eradicated in 45 of 56 strains, and the eradication rate was 80.4%. Side effects were observed in 4.8%, the majority being gastrointestinal disorders. Abnormal clinical laboratory findings were observed in 11 cases. But neither serious side effects nor serious abnormal laboratory findings were noted. The ratio of skin tissue level to serum level of CTM was 44% on average at 2 hours after administration of 400 mg of cefotiam hexetil to 10 patients. From the results of these studies, we consider cefotiam hexetil to be useful for the treatment of skin infections.