Intravenous TMP-SMZ was used to treat 19 infectious episodes in 18 patients ranging in age from 3 weeks to 13 years. Thirteen patients with various soft tissue or skeletal infections caused by Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus. Streptococcus pyogenes, or Acinetobacter anitratus were successfully treated. Three children with four episodes of CSF shunt infections due to coagulase-negative staphylococci were treated successfully also. The only treatment failures were in two newborn infants with enteric gram-negative bacterial ventriculitis. TMP-SMZ was given at a daily dose of 10 and 50 mg/kg, respectively, every six hours. The drug was administered intravenously for a mean duration of 10 days (range 4 to 32); in 11 patients this was followed by oral administration for a mean of nine days (range 2 to 18). Half-life of TMP after intravenous administration was 5 1/4 hours; that of SMA was 8 1/2 hours. Levels determined three to four days after starting therapy were generally higher than levels obtained at corresponding times after the first dose. CSF/blood TMP and SMA ratios, determined in four patients, were 0.6 and 0.5, respectively. Side effects were observed in 14 patients, and neutropenia was the most common adverse reaction. Intravenous TMP-SMZ is an effective antimicrobic agent in the treatment of infections due to susceptible organisms. The frequent side effects, although reversible and of no major clinical consequence, suggest that future use of TMP-SMZ should be monitored closely.