The in vitro activity of cefotaxime and other third-generation cephalosporins against gram-positive pathogens is generally considered to be less than that of earlier cephalosporins, such as cefazolin. A review of pooled pre-release data collected by numerous investigators and supplied by Hoechst-Roussel made it possible to evaluate the clinical and bacteriologic efficacy of cefotaxime in more than 900 infections caused by gram-positive organisms. The most commonly isolated pre-treatment organisms were Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and other streptococcal species. The overall clinical efficacy rate was 95% and the bacteriologic eradication rate was 94.5%. Side-effects were limited to rash in two, diarrhea in one and fever in one. Pain at the administration site was reported by four patients. Comparative studies with cefazolin against S. aureus showed no statistically significant differences in efficacy. The highest failure rates were seen in enterococcal urinary tract infections, as predicted by in vitro sensitivity tests. Cefotaxime appears to be a safe, effective antibiotic for the therapy of infections caused by gram-positive pathogens.