The fact that some individuals have bilateral differences in the diameter of their pupils, a condition known as anisocoria, has long been recognized by opthalmologists and neurologists. While anisocoria is generally considered to be a diagnostically important correlate of ocular lesion or aberration, there is much less agreement on its reported relationship to other clinical states, which include diabetes, multiple sclerosis, epidemic encephalitis, frontal lobe tumor [1], tumors creating pressure on the third nerve, prefrontal lobectomy, tuberculosis meningitis, cerebral beriberi, mumps [2], neural dysfunction of the diencephalon [3], altered thyroid function [4], impaired tendon reflexes [5], insufficiency of the post-ganglionic cholinergic parasympathetic fibers [6–8], palperpral fissure inequality [9], hysteria, schizophrenia, migraine, scleroderma, cardiac arrhythmia, vasomotor instability, dermography, asymmetric sweating, anhidrosis in the arms and hands [10], mental troubles in association with endocrine and vasomotor problems [11] and emotion associated with the death of a loved one [12,13]. Some authors, most prominently Lowenstein and Lowenfield [10], who support a “disease or injury” causal view of anisocoria, point out that very little research is available and that most of the relationships reported, especially with psychological states, might be spurious or at best secondary. They admit, however, that ocular injury or disease correlates in many cases of anisocoria have not yet been adequately documented, and a more systematic research approach to the phenomenon of anisocoria is needed. The series of studies reported here were intended to be an intial step towards the systematic exploration of variables associated with anisocoria. Specifically, attempts were made to identify physiological correlates of the anisocoric state and to determine whether pupillary inequality and its directionality (right pupil larger than the left or vice versa) correspond to inequality and directionality of other autonomic variables. Such an investigation of related automonic variables was deemed pertinent in view of the multitude of previously reported clinical correlates of anisocoria suggestive of autonomic imbalance.