Methods which might be useful in preventing cephalothin-induced phlebitis following intravenous administration of the buffered drug were investigated. One hundred and twenty adult orthopedic patients were assigned randomly to either a control group or one of five treatment groups. The treatment regimens studied were: addition of hydrocortisone phosphate 10 mg to each liter of intravenous fluid; addition of heparin 1,000 units to each liter of intravenous fluid; addition of heparin 500 units and hydrocortisone phosphate 1 mg to each liter of intravenous fluid; addition of heparin 1,000 units and hydrocortisone phosphate 10 mg to each liter of intravenous fluid; and filtration of intravenous solutions through a 0.22-mum inline filter. All patients in the study received intravenous buffered cephalothin at a dosage of 1 g every six hours for a minimum of 48 hours. Phlebitis was assessed every 12 hours according to predetermined criteria. Significant differences were found in the incidence of phlebitis at 48 hours between the control group and the last three study groups (see above). It is concluded that postinfusion phlebitis following cephalothin administration can be reduced by the concomitant addition of heparin and hydrocortisone to the intravenous solution or by the use of an inline 0.22-mum final filter.