<b><i>Purpose:</i></b> In the outer retina, age-related macular degeneration (AMD) results in reduced hydraulic conductivity in Bruch's membrane, possibly leading to altered water transport in retinal pigment epithelial (RPE) cells. We hypothesize that RPE cells may express aquaporin-1 (AQP1) to compensate for these changes. Therefore, we wanted to investigate the expression of AQP1 in RPE cells of human eyes with age-related maculopathy (ARM) and AMD, and eyes with tumour-associated drusen. <b><i>Methods:</i></b> Nine human eyes with ARM, 6 eyes with AMD and 9 eyes with choroidal malignant melanoma were examined for immunoreactivity to AQP1. AQP1 labelling in the RPE cells was evaluated for each drusen and grouped according to size and AQP1 labelling. AQP1 labelling in the RPE outside drusen was also evaluated. <b><i>Results:</i></b> AQP1 labelling was observed in the apical membrane of the RPE cells situated above drusen in all three groups. There was a significant association between AQP1 labelling and drusen size (p < 0.001), and AQP1 labelling was more frequently observed in large drusen. <b><i>Conclusion:</i></b> AQP1 was expressed in RPE cells covering drusen but not in RPE cells outside drusen. We suggest that AQP1 expression is upregulated in the cell membranes of RPE cells above drusen in order to alleviate the increased need for fluid transport across the growing drusen.