The rabies virus is usually transmitted to a human through the bite of an infected animal. The virus begins to replicate in the striated muscle cells at the bite site. It then spreads up the nerve to the CNS and replicates in the brain. Finally, it moves through the nerves into other tissue, including the salivary glands.

Untreated rabies almost invariably leads to life-threatening complications, including respiratory failure, peripheral vascular collapse, and central brain failure. If intensive support is provided, a number of later complications may occur, including inappropriate secretion of antidiuretic hormone, diabetes insipidus, cardiac arrhythmias, vascular instability, adult respiratory distress syndrome, GI bleeding, thrombocytopenia, and paralytic ileus. Recovery is very rare in patients who show signs of infection; when recovery does occur, it is gradual.

After an incubation period of a few days to several years, but usually 30 to 90 days, rabies typically produces local or radiating pain or burning and a sensation of cold, pruritus, and tingling at the bite site. It also produces prodromal signs and symptoms, such as a slight fever (100° to 102° F [37.8° to 38.9° C]), malaise, headache, anorexia, nausea, sore throat, and persistent loose cough. After this, the patient begins to display nervousness, anxiety, irritability, hyperesthesia, photophobia, sensitivity to loud noises, pupillary dilation, tachycardia, shallow respirations, pain and paresthesia in the bitten area, and excessive salivation, lacrimation, and perspiration.