The purpose of this study was to define the in vivo human ocular response to irritant gases. To this end, several ocular response parameters—blink rate, surface temperature, and tear production—were measured before and after ocular sulphur dioxide exposure. Blink rate and ocular surface temperature were determined by conventional techniques, while tearing was measured by an original method based on the Schirmer test. Of these irritant responses, tearing proved to be the most consistent and quantifiable. In studies using both sulphur dioxide and ammonia, the tearing response was characterized in terms of speed of onset and resolution, dose vs. concentration dependence, and effect of stimulation of one eye on the unexposed, contralateral eye. The relationship between irritant gas concentration and tearing response was defined, and the threshold for the tearing response was found to be 5ppm. sulphur dioxide and 55ppm. ammonia. Finally, the afferent pathway for the tearing response was studied using a variety of physical and chemical blocking techniques: the ocular irritant response was found to be inhibited by impermeable corneal contact lenses, but was unaffected by topical anesthetics, beta-adrenergic antagonists, prostaglandin synthesis inhibitors, and trigeminal spinal tractotomy (in individuals who had undergone this procedure as a treatment for trigeminal neuralgia). Taken together, these studies suggest that the in vivo human ocular irritant response is a neural reflex function of the trigeminal nerve initiated by specific corneal chemoreceptors, and that measurement of the tearing irritant response can be a useful adjunct to more conventional pulmonary techniques in determining threshold limit values for sensory irritants.