Thirty-four patients with osteomyelitis were treated for a mean of 32.5 days with 2 to 4 g per day of imipenem/cilastatin. Twenty-six infections involving the lower extremities were associated with accidents and prosthesis implantation, and 19 of 34 patients had more than one organism isolated. Gram-positive and gram-negative organisms were equally represented, but follow-up bone culture samples showed only 11 percent of gram-positive organisms persisted versus 23 percent of gram-negative organisms. Seventy-four percent of patients were cured or improved, and failures were related to resistant organisms and the inability to perform adequate surgical debridement. Adverse drug side effects included nausea, diarrhea, liver enzyme elevations, and neutropenia, but discontinuation of treatment was required in only three patients. Imipenem/cilastatin holds promise as monotherapy in complicated polymicrobial osteomyelitis.