A prospective randomized double-blind study comprising 118 patients was performed to evaluate the effects of doxycycline as a prophylactic antimicrobial in elective colonic surgery. Fifty-eight patients were treated and 60 were controls. 200 mg of active substance or placebo was given 4-6 hours before operation and 100 mg daily for the next five postoperative days. Levels of doxycycline in serum and tissues were determined and related to the MIC-values of the contaminants. A significantly lower incidence of abdominal wound sepsis, intra-abdominal complications and septicaemia was found in the doxycycline group (12.4%) compared to the controls (45%). The positive effects were most pronounced in the non-contaminated cases, and especially in the cases with negative wound culture at operation. In order to evaluate the effect of prophylaxis in clinical routine an open study comprising 182 patients was carried out. In the group of patients receiving adequate prophylaxis (159 patients) the abdominal wound sepsis rate was 8.1%. 11 other patients who had received doxycycline preoperatively for some time because of intra-abdominal infection developed wound sepsis in 63.4%. In 12 patients where incomplete or no prophylaxis was given, the wound sepsis rate was 33.2%. The frequency of abdominal septic complications did not differ between non-contaminated, 10.9%, and contaminated operations, 13.8%, partly because of the topical application of ampicillin in some of the patients belonging to the latter category. Preoperative treatment with doxycycline because of some intra-abdominal was evidently the single risk factor associated with a high septic complication rate. No adverse ecological effects were seen during the 19 months study.