Dimethylamine (DMA) is an important commodity chemical with many diverse industrial applications. The gas is a respiratory tract irritant with a Threshold Limit Value of 10 ppm. Male and female F-344 rats and B6C3F1 mice are being exposed to 0, 10, 50, or 175 ppm DMA for 2 years (6 h/day, 5 d/wk) to study the toxicity associated with chronic exposure to DMA. After 6 months, body weight gain, mortality, hematology, clinical chemistry, organ weights, and histopathology were assessed. Weight gain in rats and mice exposed to 175 ppm DMA was significantly reduced (5-15%) compared to controls. Otherwise, the only treatment related effects were concentration-dependent lesions confined to the nasal passages, primarily in the olfactory mucosa. At both 175 ppm and 50 ppm, there was selective destruction of the olfactory epithelial sensory cells accompanied by degeneration of the olfactory nerves. Inflammation and epithelial hyperplasia were evident in the respiratory mucosa of rats and mice exposed to 175 ppm DMA, and goblet cell hyperplasia was detected in the 175 ppm exposed rats only. No lesions were found in the 10 ppm rats and only equivocal olfactory changes in the 10 ppm mice. Thus, the only observed target organ for DMA toxicity was the epithelial lining of the nasal cavity.