Eight cases of sternal/mediastinal infection due to Enterobacter species were seen in postoperative cardiac patients during 1980 to 1981. The attack rate was 14.5% (8/55), compared to 3.7% (2/54) for an identical period in 1979 to 1980 (p less than 0.05). Cases varied in severity from fulminant, acute bacteremic infections (one death) to less severe wound infection. Late complications or recurrences were not seen. There was a hospital-wide increase, relative to all other gram-negative bacillary isolates, in Enterobacter laboratory isolations, but no increased rate of infection in any other specific surgical condition. No personnel, materials, or techniques were associated with the outbreak, and all but two environmental cultures were negative. Case-control analysis suggested that surgical complications and prophylactic cephalosporins were associated with infection. Prospectively, an additional 85 cardiac surgery patients had increased Enterobacter skin/wound colonization following perioperative prophylaxis with cephalosporin antibiotics. After introduction of barrier isolation and restriction of contacts no further mediastinitis occurred in 100 subsequent cardiac surgery patients. This study indicates that Enterobacter may be major pathogens causing post-cardiac-surgery infection not prevented by cephalosporin prophylaxis.