This two-part study was undertaken to evaluate the effect of perioperative Adriamycin on skin-graft take and adherence in an animal model. Thirty-four male Fisher rats were divided into control and experimental groups. The controls received intravenous saline, and the experimental animals received Adriamycin 6 mg/kg (LD 10) 24 hours preoperatively. Each animal was then grafted with an autogenous split-thickness skin graft on a contiguous dermal and fascial bed. Skin-graft take was judged and measured at 7 and 14 days postoperatively. The average skin-graft take for controls was 6.1 cm2 on both the dermal and fascial beds. This was significantly better than the average skin-graft take sustained by the experimental groups of 4.3 and 3.5 cm2 on the dermal and fascial beds, respectively (p less than 0.01). Another 30 animals were divided into three control and three experimental groups. They were treated with saline and Adriamycin as before, and they underwent a similar surgical procedure. Skin-graft adherence, which was measured at 12, 24, and 48 hours postoperatively, was significantly less in the experimental groups compared with the control groups at all times measured. These data suggest that a single supratherapeutic dose of Adriamycin given preoperatively decreases skin graft take in the experimental model studied and that this decrease may be the result of a concomitant decrease in graft adherence.