1. 1. The present study was undertaken to examine the hypothesis that muscarinic receptor sensitivity is increased in depression 2. 2. Pupillary responses to increasing concentrations of pilocarpine (0.08%–0.23%) given in a 2 ml solution were compared between ten male patients with major depression and a matched group of normal controls. 3. 3. Individual differences in pupil size due to anatomic variability or adrenergic tone were evaluated under conditions of maximum pupil dilation following cholinergic blockade (tropicamide, 0.5%). 4. 4. In contrast to controls, depressed patients exhibited significantly greater reductions in pupillary diameter following pilocarpine in doses between 0.095%–0.185%. This was true regardless of whether or not the results were adjusted for differences in dilated pupil size. 5. 5. These results are consistent with the idea that muscarinic sensitivity is increased in depression and indicate that depressed patients may be discriminated from controls on the basis of pupillary sensitivity to pilocarpine.