Purpose. To examine the effects of nicotine on responses from the human retina measured electrophysiologically. Methods. Electroretinogram (ERG) responses were obtained from ten healthy, visually normal adults who were nonsmokers. Nicotine (2 and 4 mg) and a placebo were administered in the form of gum 30 minutes before testing in two separate experiments. ERG responses were collected and analyzed using a full-field ERG system. Responses were recorded from one eye of each subject using a bipolar contact-lens electrode. Intensity-response curves were obtained under both dark- and light-adapted conditions. In experiment 1, both dark- and lightadapted tests were completed sequentially. In experiment 2, only light-adapted testing was performed. Intensity-response functions were analyzed using the Naka-Rushton equation. Results. In experiment 1, compared with placebo, darkadapted b-wave amplitude responses decreased significantly after chewing gum containing both 2 and 4 mg of nicotine. Under light-adapted conditions, the peak b-wave amplitude was significantly decreased after chewing gum containing 4 mg of nicotine. In experiment 2, light-adapted b-wave amplitudes were increased after 4 mg nicotine. Oscillatory potentials were measured but no significant effects under nicotine were observed. Conclusions. To the knowledge of the authors, this is the first demonstration that nicotine by itself affects responses in the human retina. These data support reports of the expression of nicotinic acetylcholine receptors in rabbit and nonhuman primate retina. © 2011 The Association for Research in Vision and Ophthalmology, Inc.