The dynamic interaction of planktonic and biofilm cells of mucoid Pseudononas aeruginosa with tobramycin and piperacillin was investigated in a chemostat system. The results indicated that planktonic and young biofilm cells of the 2-day-old chemostat culture of P. aeruginosa were susceptible to killing by chemostatcontrolled doses of either 250 ,ug of piperacillin per ml plus 5 ,ug of tobramycin per ml or 500 ,ug of piperacillin per ml plus 5 jig of tobramycin per ml. Complete eradication of the planktonic and young biofilm cells was observed after exposure of the cells to six chemostat-controlled doses of these antibiotics at 8-h intervals for 7 days. Regrowth of the organism was not observed after the termination of antibiotic therapy on day 7. A different picture was observed when antibiotic treatment was initiated on day 10 after inoculation. Viable old biofilm cells were reduced to approximately 20%o after exposure to the chemostat-controlled doses of500 jLg ofpiperacillin per ml plus 5 jig of tobramycin per ml. Complete eradication of old biofilm cells could not be achieved, and regrowth of the organism occurred after the termination of antibiotic therapy. These data suggest that young biofilm cells of mucoid P. aeruginosa can be effectively eradicated with the combination of piperacillin and tobramycin, while old biofilm cells are very resistant to these antibiotics and eradication of old biofilm cells is not achievable with the chemostat-controlled doses of piperacillin and tobramycin used in this study.