One hundred fifty-three critical care patients with documented cimetidine and antacid use were prospectively studied with serial gastric pH determinations and semiquantitative gastric fluid cultures. This study documents the abnormal gastric colonization of patients with therapeutically altered gastric acidity by hospital acquired gram negative rods (GNR). Three hundred twenty-four gastric fluid cultures from 153 patients revealed 152 (47%) positive cultures for GNR, 78 (24%) sterile specimens, and 94 (29%) positive for mixed oropharyngeal flora. One hundred forty (59%) of the 236 cultures at a pH of 4 or greater were positive for GNR. In contrast, only 12 (14%) of the 88 cultures at a pH of less than 4 were positive for GNR (p<.001). Forty-six (52%) of 88 cultures at a pH of less than 4 were sterile as compared to only 32 (14%) of 236 sterile cultures at a pH of 4 or greater (p<.001). At low pH, cultures are predominately sterile and at a pH of 4 or greater the flora dramatically changes to hospital acquired GNR. This artificially maintained reservoir of gram negative rods in the critically ill patient is a potential reservoir of organisms causing nosocomial bacteremia or pneumonia in this high risk population.