Polyhexamethylene guanidine (PHMG) is a guanidine derivative that is used as a biocidal disinfectant, often in the form of its salt polyhexamethylene guanidine hydrochloride (PHMG-HCl). PHMG-HCl is one of the cause agents of the humidifier fungicide accidents in Korea. Therefore, this study was conducted to investigate the inhalation toxicity of PHMG-HCl. The inhalation toxicity of PHMG-HCl was assessed by observing F344 rats exposed for 4 hr using the whole body chambers. The rats were exposed to the concentrations of test chemical 0, 20, 80, 160 and 280 mg/m3. Three males and three females died in the rats exposed to the concentration of 280 mg/m3. As the results of clinical signs, nasal hemorrhage, rale, decrease respiration rate, and decrease in locomotor activity were observed in the rats inhaled to the concentrations of 160 and 280 mg/m3. Animal’s appearance were overall emaciation or weakening after exposure. Nasal hemorrhage in the rats exposed to the concentration of 280 mg/m3 was observed in 2 males on the day of exposure. In the changes of body weight, the rats exposed to the concentration of 160 and 280 mg/m3 showed continuous weight loss after exposure. At necropsy, the findings of ballooning and pale discoloration of lung, and small of thymus were observed in the rats exposed to the concentration of 160 and 280 mg/m3. Based on these results, LC50 value was calculated to be 276.9 mg/m3 in both gender under the study conditions.