Some people suffer from allergic reactions after handling onions. Symptoms can include contact dermatitis, intense itching, rhinoconjunctivitis, blurred vision, bronchial asthma, sweating, and anaphylaxis. Allergic reactions may not occur when eating cooked onions, possibly due to the denaturing of the proteins from cooking.

Freshly cut onions can produce a stinging sensation in the eyes of people nearby and often uncontrollable tears. This is caused by the release of a volatile liquid, syn-propanethial-S-oxide and its aerosol, which stimulates nerves in the eye. This gas is produced by a chain of reactions which serve as a defence mechanism: chopping an onion causes damage to cells which releases enzymes called alliinases. These break down amino acid sulfoxides and generate sulfenic acids. A specific sulfenic acid, 1-propenesulfenic acid, is rapidly acted on by a second enzyme, the lacrimatory factor synthase (LFS), producing the syn-propanethial-S-oxide. This gas diffuses through the air and soon reaches the eyes, where it activates sensory neurons. Lacrimal glands produce tears to dilute and flush out the irritant. Eye irritation can be minimised by cutting onions under running water or submerged in a basin of water. Leaving the root end intact also reduces irritation as the onion base has a higher concentration of sulphur compounds than the rest of the bulb.

The amount of sulfenic acids and lacrimal factor released and the irritation effect differs among Allium species. In 2008, the New Zealand Institute for Crop and Food Research created "no tears" onions by genetic modification to prevent the synthesis of lachrymatory factor synthase in onions. One study suggests that consumers prefer the flavour of onions with lower LFS content.