Local irrigation with gentamicin sulfate represents a possible substitute for neomycin sulfate, used for many years but now no longer available for use as an irrigation fluid. In this investigation, mediastinal irrigation with gentamicin was used in 12 patients who had experienced problems after a heart operation. The regimen employed for mediastinal irrigation with gentamicin was equipotent with that using neomycin. We sought to determine the degree of absorption and risk of either inadequate or toxic blood levels that might follow gentamicin absorption. Irrigation periods were short, ranging from one to four days and determined by measurements of plasma gentamicin concentration using radioimmunoassay evaluation. Systemic gentamicin absorption occurred in all patients. Toxic levels of higher than 8.0 micrograms/mL occurred and were size related, ie, correlated with smaller body weight and surface area, and sex related, ie, female sex. Larger-sized patients often had inadequate levels. Despite the potential risk from toxic blood levels, major increases in serum creatinine levels were not seen. These findings suggest that monitoring of plasma gentamicin levels during mediastinal irrigation with gentamicin is mandatory to avoid both inadequate treatment and toxicity.